Objective To explore the differences in cytotoxicity, antioxidant, and hypoglycemic activities of resveratrol, oxy-resveratrol, and piceatannol, three stilbene compounds with similar structures.Methods The cytotoxicity, extracellular/intracellular antioxidant activity, and hypoglycemic activity of the three compounds are analyzed by Cell Counting Kit-8 (CCK-8), total antioxidant activity, cellular antioxidant stress ability, intracellular reactive oxygen species (ROS) content, cellular antioxidant activity (CAA) assay, and α-glucosidase inhibitory activity.Results Compared with oxy-resveratrol and resveratrol, piceatannol shows lower cytotoxicity, better extracellular antioxidant activity, and α-glucosidase inhibitory activity. All three stilbenes effectively mitigate the oxidative stress damage of HepG2 cells induced by H₂O₂ solution and reduce the ROS content in HepG2 cells in a dose-dependent manner. Oxy-resveratrol demonstrates a stronger capacity to inhibit the generation of oxygen free radicals induced by ABAP in HepG2 cells.Conclusion The three stilbene compounds all have high antioxidant activity and hypoglycemic activity.