<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0206</schemaVersion>

    <documentType>3</documentType>

    <periodOfReport>2022-03-01</periodOfReport>

    <noSecuritiesOwned>1</noSecuritiesOwned>

    <issuer>
        <issuerCik>0001604191</issuerCik>
        <issuerName>First Wave BioPharma, Inc.</issuerName>
        <issuerTradingSymbol>FWBI</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001697536</rptOwnerCik>
            <rptOwnerName>Romano Sarah</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O FIRST WAVE BIOPHARMA, INC.</rptOwnerStreet1>
            <rptOwnerStreet2>777 YAMATO ROAD, SUITE 502</rptOwnerStreet2>
            <rptOwnerCity>BOCA RATON</rptOwnerCity>
            <rptOwnerState>FL</rptOwnerState>
            <rptOwnerZipCode>33431</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isOfficer>true</isOfficer>
            <officerTitle>Chief Financial Officer</officerTitle>
        </reportingOwnerRelationship>
    </reportingOwner>

    <ownerSignature>
        <signatureName>/s/ Sarah Romano</signatureName>
        <signatureDate>2022-03-02</signatureDate>
    </ownerSignature>
</ownershipDocument>
