<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2025 Workiva-->
<!--r:64617dd3-a645-42f0-b1b7-961ae07fdb75,g:d8b66b8c-e339-44d3-9a90-56485c8b752d-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:roleRef roleURI="http://www.vistagen.com/role/CONDENSEDCONSOLIDATEDBALANCESHEETS" xlink:type="simple" xlink:href="vtgn-20250630.xsd#CONDENSEDCONSOLIDATEDBALANCESHEETS"/>
  <link:calculationLink xlink:role="http://www.vistagen.com/role/CONDENSEDCONSOLIDATEDBALANCESHEETS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Assets_56aa3e1d-6c11-4e34-b114-b9f03221f0d1" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Assets"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_6d1249ce-7d21-4a39-bda1-d4a58f6277e2" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_56aa3e1d-6c11-4e34-b114-b9f03221f0d1" xlink:to="loc_us-gaap_AssetsCurrent_6d1249ce-7d21-4a39-bda1-d4a58f6277e2" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_5c12520d-1deb-4a75-af12-d7196586b14e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_56aa3e1d-6c11-4e34-b114-b9f03221f0d1" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_5c12520d-1deb-4a75-af12-d7196586b14e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAsset_6c9a0fca-97bf-445f-a96c-1c7c1e8d7687" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseRightOfUseAsset"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_56aa3e1d-6c11-4e34-b114-b9f03221f0d1" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAsset_6c9a0fca-97bf-445f-a96c-1c7c1e8d7687" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherAssetsNoncurrent_2a8978e1-e586-492f-9374-3c7ec6e50a75" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherAssetsNoncurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Assets_56aa3e1d-6c11-4e34-b114-b9f03221f0d1" xlink:to="loc_us-gaap_OtherAssetsNoncurrent_2a8978e1-e586-492f-9374-3c7ec6e50a75" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsCurrent_f18a72ef-32d4-45d8-a0d3-356b3b444ab3" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_06eb2c3b-12b3-4a24-9b3b-f5ffa96084ae" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PrepaidExpenseAndOtherAssetsCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_f18a72ef-32d4-45d8-a0d3-356b3b444ab3" xlink:to="loc_us-gaap_PrepaidExpenseAndOtherAssetsCurrent_06eb2c3b-12b3-4a24-9b3b-f5ffa96084ae" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_7d77338f-2fbc-4810-9732-44dfbc675b30" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsAtCarryingValue"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_f18a72ef-32d4-45d8-a0d3-356b3b444ab3" xlink:to="loc_us-gaap_CashAndCashEquivalentsAtCarryingValue_7d77338f-2fbc-4810-9732-44dfbc675b30" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_8dd0bfe9-c393-4af1-97db-be0d94d7adea" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsCurrent_f18a72ef-32d4-45d8-a0d3-356b3b444ab3" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent_8dd0bfe9-c393-4af1-97db-be0d94d7adea" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_d606ea17-55d7-4526-9bda-d9c8e7913ba5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccruedLiabilitiesCurrent_9eea6e2a-366f-4d9e-ae19-f7ea26d3a26b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccruedLiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_d606ea17-55d7-4526-9bda-d9c8e7913ba5" xlink:to="loc_us-gaap_AccruedLiabilitiesCurrent_9eea6e2a-366f-4d9e-ae19-f7ea26d3a26b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityCurrent_8710dbe7-ecf3-4617-a5cd-5b65a3599d6d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityCurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_d606ea17-55d7-4526-9bda-d9c8e7913ba5" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityCurrent_8710dbe7-ecf3-4617-a5cd-5b65a3599d6d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityCurrent_fef2204e-032e-4b42-8988-ae8d7e0311e9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityCurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_d606ea17-55d7-4526-9bda-d9c8e7913ba5" xlink:to="loc_us-gaap_OperatingLeaseLiabilityCurrent_fef2204e-032e-4b42-8988-ae8d7e0311e9" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsPayableCurrent_c8041505-ca35-4d36-b0f0-9140845fe015" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccountsPayableCurrent"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_d606ea17-55d7-4526-9bda-d9c8e7913ba5" xlink:to="loc_us-gaap_AccountsPayableCurrent_c8041505-ca35-4d36-b0f0-9140845fe015" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NotesPayableCurrent_c6a16117-fec4-4860-90fa-65482754aaab" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NotesPayableCurrent"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesCurrent_d606ea17-55d7-4526-9bda-d9c8e7913ba5" xlink:to="loc_us-gaap_NotesPayableCurrent_c6a16117-fec4-4860-90fa-65482754aaab" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_dcd792e6-a7a6-443c-934f-090144744459" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Liabilities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesCurrent_bfa74173-631d-424b-a77e-208b5c519f84" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesCurrent"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_dcd792e6-a7a6-443c-934f-090144744459" xlink:to="loc_us-gaap_LiabilitiesCurrent_bfa74173-631d-424b-a77e-208b5c519f84" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_2bdb173a-83f4-481f-b502-32b598a12fee" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ContractWithCustomerLiabilityNoncurrent"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_dcd792e6-a7a6-443c-934f-090144744459" xlink:to="loc_us-gaap_ContractWithCustomerLiabilityNoncurrent_2bdb173a-83f4-481f-b502-32b598a12fee" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_953a9f9a-9abe-4a14-bc73-0a5d47acdd89" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseLiabilityNoncurrent"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_Liabilities_dcd792e6-a7a6-443c-934f-090144744459" xlink:to="loc_us-gaap_OperatingLeaseLiabilityNoncurrent_953a9f9a-9abe-4a14-bc73-0a5d47acdd89" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_8b1ce11f-7f8b-4b79-adf7-0775c7fa3258" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockCommonValue_d1988ef4-47dc-44f5-a698-8a95590751f7" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_TreasuryStockCommonValue"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8b1ce11f-7f8b-4b79-adf7-0775c7fa3258" xlink:to="loc_us-gaap_TreasuryStockCommonValue_d1988ef4-47dc-44f5-a698-8a95590751f7" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsAccumulatedDeficit_98ccdaa5-3a9a-41f8-bf2b-a18ee85f1470" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RetainedEarningsAccumulatedDeficit"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8b1ce11f-7f8b-4b79-adf7-0775c7fa3258" xlink:to="loc_us-gaap_RetainedEarningsAccumulatedDeficit_98ccdaa5-3a9a-41f8-bf2b-a18ee85f1470" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockValue_b0738fa0-28d6-45ec-ad2d-4558e64db7ec" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PreferredStockValue"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8b1ce11f-7f8b-4b79-adf7-0775c7fa3258" xlink:to="loc_us-gaap_PreferredStockValue_b0738fa0-28d6-45ec-ad2d-4558e64db7ec" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockValue_2e897342-a6af-49b7-9daa-4e12fd566bf5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommonStockValue"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8b1ce11f-7f8b-4b79-adf7-0775c7fa3258" xlink:to="loc_us-gaap_CommonStockValue_2e897342-a6af-49b7-9daa-4e12fd566bf5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapital_8da1e1bf-d987-45b5-a508-0c92d713dca5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AdditionalPaidInCapital"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8b1ce11f-7f8b-4b79-adf7-0775c7fa3258" xlink:to="loc_us-gaap_AdditionalPaidInCapital_8da1e1bf-d987-45b5-a508-0c92d713dca5" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_52758d3f-0501-4a03-8909-d733eb76176b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_StockholdersEquity_8b1ce11f-7f8b-4b79-adf7-0775c7fa3258" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeLossNetOfTax_52758d3f-0501-4a03-8909-d733eb76176b" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesAndStockholdersEquity_80a3b350-bb15-44b6-b320-5367c856d090" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_LiabilitiesAndStockholdersEquity"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_6ae8c171-c23e-412b-bdbc-fd382dcc7672" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_StockholdersEquity"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_80a3b350-bb15-44b6-b320-5367c856d090" xlink:to="loc_us-gaap_StockholdersEquity_6ae8c171-c23e-412b-bdbc-fd382dcc7672" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Liabilities_82e9e1a7-296d-4355-8ba6-a27ebf6b2864" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_Liabilities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_80a3b350-bb15-44b6-b320-5367c856d090" xlink:to="loc_us-gaap_Liabilities_82e9e1a7-296d-4355-8ba6-a27ebf6b2864" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommitmentsAndContingencies_d27ac022-92ea-49b7-a7fa-7e6913bd0df9" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CommitmentsAndContingencies"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_LiabilitiesAndStockholdersEquity_80a3b350-bb15-44b6-b320-5367c856d090" xlink:to="loc_us-gaap_CommitmentsAndContingencies_d27ac022-92ea-49b7-a7fa-7e6913bd0df9" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.vistagen.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" xlink:type="simple" xlink:href="vtgn-20250630.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS"/>
  <link:calculationLink xlink:role="http://www.vistagen.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONSANDCOMPREHENSIVELOSS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_dc941538-f524-412b-94de-0f9c5878a0b5" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_2c321daa-6aa5-41f9-ad80-7337aa371ea4" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_dc941538-f524-412b-94de-0f9c5878a0b5" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_2c321daa-6aa5-41f9-ad80-7337aa371ea4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_b2cb1c13-36f1-441b-a661-bede6019e71a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetIncomeLoss_dc941538-f524-412b-94de-0f9c5878a0b5" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_b2cb1c13-36f1-441b-a661-bede6019e71a" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_2404581f-768d-45d9-a15c-0b8b98fac229" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingExpenses"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_f4c9ad8b-80af-4b65-b042-46792284a12c" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_2404581f-768d-45d9-a15c-0b8b98fac229" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_f4c9ad8b-80af-4b65-b042-46792284a12c" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_3177b4fc-2556-49f0-85de-48299a50f34f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingExpenses_2404581f-768d-45d9-a15c-0b8b98fac229" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_3177b4fc-2556-49f0-85de-48299a50f34f" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_4ada8631-bea4-4ad8-9acd-f57d9a01344a" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_7f41b595-b9c3-4ded-b0a0-6a2057f9ff19" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_4ada8631-bea4-4ad8-9acd-f57d9a01344a" xlink:to="loc_us-gaap_OperatingIncomeLoss_7f41b595-b9c3-4ded-b0a0-6a2057f9ff19" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeExpenseNonoperatingNet_678f3ad3-4005-4bbb-a047-778d48497254" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_InterestIncomeExpenseNonoperatingNet"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_4ada8631-bea4-4ad8-9acd-f57d9a01344a" xlink:to="loc_us-gaap_InterestIncomeExpenseNonoperatingNet_678f3ad3-4005-4bbb-a047-778d48497254" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_642d5939-7574-413a-a6a3-cb3e3b121e41" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_4ada8631-bea4-4ad8-9acd-f57d9a01344a" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_642d5939-7574-413a-a6a3-cb3e3b121e41" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_dfa68ea3-944d-4393-9f6e-12ea76faf53f" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_59e25954-e5ab-474e-8276-0c43ba373a62" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_dfa68ea3-944d-4393-9f6e-12ea76faf53f" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerIncludingAssessedTax_59e25954-e5ab-474e-8276-0c43ba373a62" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpenses_677b4e30-ea98-43df-8c30-7de3a3ba6e96" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingExpenses"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_OperatingIncomeLoss_dfa68ea3-944d-4393-9f6e-12ea76faf53f" xlink:to="loc_us-gaap_OperatingExpenses_677b4e30-ea98-43df-8c30-7de3a3ba6e96" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ComprehensiveIncomeNetOfTax_3662af67-14bc-44a0-8c1c-accd5f3935ba" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ComprehensiveIncomeNetOfTax"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_8f6643ca-d70c-4f4e-ae06-3de086541b9e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_3662af67-14bc-44a0-8c1c-accd5f3935ba" xlink:to="loc_us-gaap_OtherComprehensiveIncomeLossAvailableForSaleSecuritiesAdjustmentNetOfTax_8f6643ca-d70c-4f4e-ae06-3de086541b9e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_51f1e6e8-e96e-4f91-8ff3-a48189579440" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_ComprehensiveIncomeNetOfTax_3662af67-14bc-44a0-8c1c-accd5f3935ba" xlink:to="loc_us-gaap_NetIncomeLoss_51f1e6e8-e96e-4f91-8ff3-a48189579440" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.vistagen.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS" xlink:type="simple" xlink:href="vtgn-20250630.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS"/>
  <link:calculationLink xlink:role="http://www.vistagen.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFCASHFLOWS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_03daa5db-3ff3-42dc-99c7-96ea661e2693" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_6fb8e9ab-7df7-4264-bb94-438cbc270867" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_03daa5db-3ff3-42dc-99c7-96ea661e2693" xlink:to="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_6fb8e9ab-7df7-4264-bb94-438cbc270867" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_8affdb9a-24ce-4ccc-a8a7-839b369f7dbe" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_03daa5db-3ff3-42dc-99c7-96ea661e2693" xlink:to="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_8affdb9a-24ce-4ccc-a8a7-839b369f7dbe" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_ad9c399c-4805-467c-b94e-75dfe7790335" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_CashCashEquivalentsRestrictedCashAndRestrictedCashEquivalentsPeriodIncreaseDecreaseIncludingExchangeRateEffect_03daa5db-3ff3-42dc-99c7-96ea661e2693" xlink:to="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_ad9c399c-4805-467c-b94e-75dfe7790335" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInOperatingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_d40df3de-7772-4be4-b067-8c5ce36d988e" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInContractWithCustomerLiability"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_us-gaap_IncreaseDecreaseInContractWithCustomerLiability_d40df3de-7772-4be4-b067-8c5ce36d988e" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_5356f348-0cbd-4030-9be4-aaafd47a5cac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetIncomeLoss"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_us-gaap_NetIncomeLoss_5356f348-0cbd-4030-9be4-aaafd47a5cac" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities_26090127-bc81-4a93-a951-1edfed1a0633" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_us-gaap_IncreaseDecreaseInAccountsPayableAndAccruedLiabilities_26090127-bc81-4a93-a951-1edfed1a0633" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DepreciationDepletionAndAmortization_1345952d-cf10-424d-bf6d-ba1b4ed6da95" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_DepreciationDepletionAndAmortization"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_us-gaap_DepreciationDepletionAndAmortization_1345952d-cf10-424d-bf6d-ba1b4ed6da95" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensation_14cfe2d9-23f7-4c52-ac89-e00f1318be98" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ShareBasedCompensation"/>
    <link:calculationArc order="5" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_us-gaap_ShareBasedCompensation_14cfe2d9-23f7-4c52-ac89-e00f1318be98" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_b11cd6e6-30ab-426b-aab5-ddea6692f387" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense"/>
    <link:calculationArc order="6" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_us-gaap_OperatingLeaseRightOfUseAssetAmortizationExpense_b11cd6e6-30ab-426b-aab5-ddea6692f387" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_13a7ae86-2e41-4f88-b4df-e4cf64beaf63" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets"/>
    <link:calculationArc order="7" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_us-gaap_IncreaseDecreaseInPrepaidDeferredExpenseAndOtherAssets_13a7ae86-2e41-4f88-b4df-e4cf64beaf63" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInOperatingLeaseLiability_d6b324f9-9e63-4141-bbdc-a72a12b6aa6d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInOperatingLeaseLiability"/>
    <link:calculationArc order="8" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_us-gaap_IncreaseDecreaseInOperatingLeaseLiability_d6b324f9-9e63-4141-bbdc-a72a12b6aa6d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_vtgn_AccretionOnMarketableSecurities_97be2c9b-eaa6-4b73-b2b6-f16a34eb5718" xlink:href="vtgn-20250630.xsd#vtgn_AccretionOnMarketableSecurities"/>
    <link:calculationArc order="9" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_vtgn_AccretionOnMarketableSecurities_97be2c9b-eaa6-4b73-b2b6-f16a34eb5718" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInOtherOperatingAssets_b7ff0141-1e7c-47d9-857f-7122876bd754" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_IncreaseDecreaseInOtherOperatingAssets"/>
    <link:calculationArc order="10" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_us-gaap_IncreaseDecreaseInOtherOperatingAssets_b7ff0141-1e7c-47d9-857f-7122876bd754" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_vtgn_NonCashInterestExpense_ccd00ff7-e3ef-4160-bf00-15ce9820b1f4" xlink:href="vtgn-20250630.xsd#vtgn_NonCashInterestExpense"/>
    <link:calculationArc order="11" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInOperatingActivities_c27c0afe-7674-4589-9c68-61f41f482285" xlink:to="loc_vtgn_NonCashInterestExpense_ccd00ff7-e3ef-4160-bf00-15ce9820b1f4" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_8bf3dd60-c88d-43f7-b410-38c3680c1470" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInFinancingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_b00224b2-4596-44c0-986a-e7a8c4ee2894" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_8bf3dd60-c88d-43f7-b410-38c3680c1470" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfCommonStock_b00224b2-4596-44c0-986a-e7a8c4ee2894" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromStockPlans_975309fc-a8fb-4383-aa92-b633e4243130" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromStockPlans"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_8bf3dd60-c88d-43f7-b410-38c3680c1470" xlink:to="loc_us-gaap_ProceedsFromStockPlans_975309fc-a8fb-4383-aa92-b633e4243130" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfNotesPayable_eb0b8b78-133c-4cc7-b9dc-83180fe622f0" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_RepaymentsOfNotesPayable"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_8bf3dd60-c88d-43f7-b410-38c3680c1470" xlink:to="loc_us-gaap_RepaymentsOfNotesPayable_eb0b8b78-133c-4cc7-b9dc-83180fe622f0" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromNotesPayable_dce90949-e2f5-443d-b470-078efced1483" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromNotesPayable"/>
    <link:calculationArc order="4" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInFinancingActivities_8bf3dd60-c88d-43f7-b410-38c3680c1470" xlink:to="loc_us-gaap_ProceedsFromNotesPayable_dce90949-e2f5-443d-b470-078efced1483" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_4252ff07-a257-4bda-9ab4-2b503ae5a383" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_NetCashProvidedByUsedInInvestingActivities"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireMachineryAndEquipment_4094e729-5827-4f3e-afcf-0decb659e6da" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquireMachineryAndEquipment"/>
    <link:calculationArc order="1" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_4252ff07-a257-4bda-9ab4-2b503ae5a383" xlink:to="loc_us-gaap_PaymentsToAcquireMachineryAndEquipment_4094e729-5827-4f3e-afcf-0decb659e6da" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_5a60b9ab-5bcd-41fc-adb0-2e1162363cac" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt"/>
    <link:calculationArc order="2" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_4252ff07-a257-4bda-9ab4-2b503ae5a383" xlink:to="loc_us-gaap_PaymentsToAcquireAvailableForSaleSecuritiesDebt_5a60b9ab-5bcd-41fc-adb0-2e1162363cac" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities_e5e6379e-3a1f-4aaa-a7c9-c1857471cb34" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities"/>
    <link:calculationArc order="3" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_NetCashProvidedByUsedInInvestingActivities_4252ff07-a257-4bda-9ab4-2b503ae5a383" xlink:to="loc_us-gaap_ProceedsFromSaleAndMaturityOfMarketableSecurities_e5e6379e-3a1f-4aaa-a7c9-c1857471cb34" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.vistagen.com/role/FairValueMeasurementsCashCashEquivalentsandMarketableSecuritiesDetails" xlink:type="simple" xlink:href="vtgn-20250630.xsd#FairValueMeasurementsCashCashEquivalentsandMarketableSecuritiesDetails"/>
  <link:calculationLink xlink:role="http://www.vistagen.com/role/FairValueMeasurementsCashCashEquivalentsandMarketableSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_8de6102a-cadc-4cac-8c78-44efa234145d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_adc5bf2c-6b44-46f9-9f89-b6975269f77d" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_8de6102a-cadc-4cac-8c78-44efa234145d" xlink:to="loc_us-gaap_CashAndCashEquivalentsFairValueDisclosure_adc5bf2c-6b44-46f9-9f89-b6975269f77d" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_6a0db436-f0cd-4490-9600-4643addc269b" xlink:href="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_us-gaap_AssetsFairValueDisclosure_8de6102a-cadc-4cac-8c78-44efa234145d" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_6a0db436-f0cd-4490-9600-4643addc269b" xlink:type="arc"/>
  </link:calculationLink>
  <link:roleRef roleURI="http://www.vistagen.com/role/FairValueMeasurementsMarketableSecuritiesDetails" xlink:type="simple" xlink:href="vtgn-20250630.xsd#FairValueMeasurementsMarketableSecuritiesDetails"/>
  <link:calculationLink xlink:role="http://www.vistagen.com/role/FairValueMeasurementsMarketableSecuritiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAmortizedCost_a55f5aff-b4b6-41b2-b78a-5a24306b0dd8" xlink:href="vtgn-20250630.xsd#vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAmortizedCost"/>
    <link:loc xlink:type="locator" xlink:label="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalents_1f38342c-7960-4eea-bca5-99754db740c3" xlink:href="vtgn-20250630.xsd#vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalents"/>
    <link:calculationArc order="1" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAmortizedCost_a55f5aff-b4b6-41b2-b78a-5a24306b0dd8" xlink:to="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalents_1f38342c-7960-4eea-bca5-99754db740c3" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAccumulatedGrossUnrealizedLossBeforeTax_bc7c4aa8-8d5f-4d6e-bcd0-2e864c9fb493" xlink:href="vtgn-20250630.xsd#vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:calculationArc order="2" weight="1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAmortizedCost_a55f5aff-b4b6-41b2-b78a-5a24306b0dd8" xlink:to="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAccumulatedGrossUnrealizedLossBeforeTax_bc7c4aa8-8d5f-4d6e-bcd0-2e864c9fb493" xlink:type="arc"/>
    <link:loc xlink:type="locator" xlink:label="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAccumulatedGrossUnrealizedGain_0ffae776-830f-45c3-9c2e-5a33190aa29e" xlink:href="vtgn-20250630.xsd#vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAccumulatedGrossUnrealizedGain"/>
    <link:calculationArc order="3" weight="-1.0" xlink:arcrole="http://www.xbrl.org/2003/arcrole/summation-item" xlink:from="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAmortizedCost_a55f5aff-b4b6-41b2-b78a-5a24306b0dd8" xlink:to="loc_vtgn_DebtSecuritiesAvailableForSaleAndCashAndCashEquivalentsAccumulatedGrossUnrealizedGain_0ffae776-830f-45c3-9c2e-5a33190aa29e" xlink:type="arc"/>
  </link:calculationLink>
</link:linkbase>
