Sweet potato (Ipomoea batatas L.) is widely used in Indonesia and other countries as a traditional medicine for the treatment of diabetes mellitus (DM). The MeOH extract of white skinned sweet potatoes (WSSP) was administered orally in doses of 100 and 200 mg/kg body weight in streptozotocin (STZ)-induced diabetic rats. Experimental diabetes was induced by a single dose of STZ (45 mg/kg, i.p.) injection. Oxidative stress was measured by tissue lipid peroxide (LPO) levels, serum aspartate transaminase (AST), alanine transaminase (ALT), total triglyceride (TG), total cholesterol (TC) and by antioxidative enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase in the liver. An increase in blood glucose, LPO level, AST, ALT, TG and TC levels was observed in the STZ-induced diabetic rats. Administration of MeOH extract of WSSP at a dose of 200 mg/kg for two weeks caused a significant reduction in blood glucose, LPO levels, AST, ALT, TG and TC levels in the STZ-induced diabetic rats. Furthermore, oral administration of MeOH extract showed significant improvement in the activities of antioxidant enzymes (SOD, GPx, and CAT) compared to STZ-induced diabetic rats. In conclusion, the obtained results clearly indicate the role of oxidative stress in the induction of diabetes, and that the protective effects of MeOH extracts of WSSP could be used to benefit diabetic patients.