OBJECTIVE: To virtually screen potential α-glycosidase inhibitor ingredients from C. mori and F. mori, and to provide reference for finding out new type α-glycosidase inhibitor ingredient. METHODS: Surflex-Dock module of Sybyl-x 2.0 molecular simulation software was used to perform the docking of small molecule compound, which was from the ingredients of C. mori and F. mori as ligand stated in literatures, with α-glycosidase. Total score of affinity scoring function was equal to 7 as the threshold value, to judge potential α-glycosidase inhibitor ingredient in C. mori and F. mori. RESULTS: After 70 small molecule compounds docked with α-glycosidase, 10 compounds showed binding activity (Total score≥7.00). Among them, moracin M-3′ -O-β-D-glucopyranoside, 5,7,2′ -trihydroxyflavanone-4′ -O-β-D-glucoside, mulberroside A, resveratrol-4,3′ -di-O-β-D-glucopyranoside and 1,4-dideoxy-1,4-imino-(2-O-β-D-glucopyranosyl)-D-arabinitol had higher binding activity with α-glycosidase (Total score>8.00). CONCLUSIONS: Multi-constituents of C. mori and F. Mori show potential α-glycosidase inhibitory activity. The method is a kind of highly targeted, rapid and efficient approach to discover α-glycosidase inhibitor from traditional Chinese medicine.