In-vitro experiments to investigate the hypoglycemic effect of oxyresveratrol (OXY) through evaluation of the antioxidant activity of OXY and characterization of the mechanisms underlying its inhibitory effects on key digestive enzymes. For pharmacological validation, a type 2 diabetes mellitus (T2DM) rat model was established through high-fat/high-sucrose diet feeding combined with streptozotocin injection. Rats were orally administered OXY daily for 28 consecutive days, during which body weight and various physiological and biochemical parameters were monitored and recorded. Histopathological examinations were performed on hepatic and renal tissues to assess organ-specific therapeutic effects. The half-maximal inhibitory concentrations (IC50) of OXY for DPPH and ABTS+ radical scavenging were 7.139 and 16.59 μg•mL–1, respectively. OXY inhibited α-amylase in a dose-dependent manner, with an IC50 value of 1.41 mg•mL–1. α-Glucosidase was inhibited by OXY in a non-competitive manner, with an IC50 of 66.59 μg•mL–1 and a Ki value of 60.82 μg•mL–1. In animal experiments, high-dose OXY intervention reduced the levels of fasting blood glucose, fasting insulin, triglycerides, total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase, alanine aminotransferase, advanced glycation end products, malondialdehyde, area under the curve, homeostasis model assessment of insulin resistance, and GSK-3β by 32.1%, 19.52%, 25.13%, 21.29%, 32.71%, 21.39%, 28.9%, 10.13%, 31.37%, 17.52%, 39.32%, and 13.16%, respectively, compared with the model group (P<0.05). Meanwhile, the levels of glutathione peroxidase, superoxide dismutase, and GYS2 expression were increased by 40.2%, 26.24%, and 18.37%, respectively (P<0.05). Histopathological examination revealed that OXY improved hepatic steatosis, inflammatory cell infiltration, and vacuolation in renal tubular epithelial cells. Collectively, these findings demonstrate that OXY exerts hypoglycemic effects and the potential to mitigate T2DM-related pathological manifestations, providing a theoretical foundation for its development and application in natural product-derived therapeutics.