Didymin inhibited α-glucosidase, activated the insulin-signaling pathway, and improved insulin sensitivity. It showed potent inhibitory activity against the key enzymes involved in diabetes mellitus, including protein tyrosine phosphatase 1B (PTP1B), α- glucosidase, advanced glycation end products (AGEs), and aldose reductase (AR). This evidence concerns the gene AKR1B1 and diabetes mellitus.