This preclinical study compared the antioxidant and hypoglycemic effects of an ethanol extract from Engelhardia roxburghiana leaves (E-LERW) to its main component, astilbin, using in vitro assays and an alloxan-induced diabetic mouse model. The extract showed stronger antioxidant and α-glucosidase inhibitory activity in vitro, and in vivo, it reduced hyperglycemia, improved glucose tolerance, and protected organs, though its hypoglycemic effect was similar to astilbin.