Oxidative stress plays an important role in the pathogenesis of various diabetic complications and small intestine is vulnerable to damage resulting in morphological and functional changes. In this study, the effects of Asystasia gangetica leaf extract (AGLE) on oxidative stress status in small intestine of diabetic rats were examined. The leaves of Asystasia gangetica was extracted with 70% ethanol. Oral administration of AGLE once daily (100 mg/kg and 200 mg/kg b.w.) for 28 days to diabetic rats significantly (P < 0.05) increased antioxidant levels of catalase, superoxide dismutase, glutathione peroxidase, glutathione, GSSH, carbohydrate metabolizing enzyme, glucose-6-phosphate dehydrogenase. The increased levels of protein carbonyl content, lipid peroxidation and xanthine oxidase/xanthine dehydrogenase in diabetic rats were reverted back to near normal levels on treatment with AGLE. Both doses of AGLE offered significant activity (P < 0.01) against oxidative damage and were comparable with standard, glibenclamide. The results revealed the occurrence of oxidative stress in small intestine during diabetes and suggest the potential of AGLE as an antioxidant in protecting the tissue defense system against oxidative damage in streptozotocin-induced diabetes.