The objectives of this study were to identify peptides that inhibit α-glucosidase using a quantitative structure-activity relationship (QSAR) screening method and a database of silkworm peptides. This study compared the docking characteristics of several peptides with high inhibitory activity against α-glucosidase and summarized the molecular mechanisms by which the silkworm peptides affected α-glucosidase. Four peptides that strongly inhibited α-glucosidase were obtained: Gln-Pro-Gly-Arg with IC50 at 65.8 μmol/L, Ser-Gln-Ser-Pro-Ala at 20 μmol/L, Gln-Pro-Pro-Thr at 560 μmol/L and Asn-Ser-Pro-Arg at 205 μmol/L. Studies docking the peptides to the active site of α-glucosidase (PDB ID: 2QMJ) showed that a common characteristic was Lys776 in 2QMJ, which could be a critical target for α-glucosidase trapping of inhibitory peptides. The results revealed that the four peptides, especially Ser-Gln-Ser-Pro-Ala, could be potential drugs for treating diabetes.