The　inhibition　of　alpha-glucosidase　decreases　postprandial　blood　glucose　and　therefore　plays　an　important　role　in　the　treatment　of　type　2　diabetes　mellitus.　The　present　study　investigated　and　characterized　a　peptide　fraction　of　sericin　hydrolysate,　the　kinetics　of　peptide-induced　inhibition　of　a-glucosidase,　and　the　interaction　mechanism　between　the　peptides　and　alpha-glucosidase.　The　fraction　that　eluted　with　0.4　M　NaCl　(F5-SPs)　on　a　DEAE-cellulose　column　exhibited　significant　inhibitory　activity　with　an　IC50　of　41　+/-　1.94　mu　g　mL(-1).　A　kinetics　analysis　revealed　that　the　F5-SP-induced　inhibition　was　a　reversible　and　parabolic　mixed-type　inhibition　with　a　K-i　value　of　86.63　+/-　0.014　mu　g　mL(-1).　F5-SPs　can　bind　to　alpha-glucosidase　at　multiple　sites　to　alter　the　conformation　of　a-glucosidase.　F5-SPs　were　found　to　be　rich　in　Gly,　Ser,　Glu,　Tyr,　Arg,　and　Pro,　and　had　a　sericin-conserved　sequence　SEDSSEVDIDLGNLG,　as　analyzed　by　Nano　LC-MS/MS.　Fluorescence　spectra　analysis　showed　that　F5-SPs　quenched　the　intrinsic　fluorescence　of　alpha-glucosidase　by　a　static　quenching　mechanism,　and　circular　dichroism　analysis　suggested　that　the　binding　of　F5-SPs　to　alpha-glucosidase　resulted　in　the　alteration　of　the　secondary　structure　of　an　enzyme.　The　results　of　this　study　support　the　dietary　recommendation　of　F5-SPs　for　the　treatment　of　type　2　diabetes.