Daidzein　(Dai)　exhibits　a　variety　of　pharmacologic　actions.　However,　the　low　solubility　and　high　crystallinity　limit　the　bioavailability　of　daidzein.　Therefore,　the　self-microemulsion　drug　delivery　system　(SMEDDS)　was　introduced　to　increase　the　solubility　of　daidzein　and　avoid　the　first　pass　effect.　Whey　protein　isolate　(WPI)　was　added　as　a　precipitation　inhibitor　to　SMEDDS　(WD-SMEDDS)　to　inhibit　daidzein　crystallization　and　improve　system　stability.　The　final　formulation　was　TPGS　and　Tween　20　as　mixed　surfactants,　PEG400　as　cosurfactant　and　ethyl　oleate　as　oil　phase　to　prepare　WD-SMEDDS.　The　stability　studies　revealed　that　mixed　surfactants　were　superior　to　single,　and　remained　stable　for　at　least　3　months.　WD-SMEDDS　showed　excellent　dissolution　behavior　that　more　than　90%　and　80%　of　daidzein　was　released　in　pH　6.8　and　pH　1.2,　respectively.　Therefore,　protein-based　SMEDDS　might　be　an　effective　strategy　for　the　oral　administration　of　Dai　and　would　be　a　potential　system　to　deliver　hydrophobic　bioactive　compounds.　©　2020　Elsevier　Ltd