Abnormal regulation of glucose and impaired carbohydrate utilization that result from a defective or deficient insulin are the key pathogenic events in type 2 diabetes mellitus (T2DM). The present study was hypothesized to investigate the beneficial effects of hesperidin and naringin on hyperglycemia-induced oxidative damage in HFD/STZ-induced diabetic rats. Diabetes was induced by feeding rats with an HFD for 2 weeks followed by an intraperitoneal injection of STZ (35 mg/kg body weight). An oral dose of 50mg/kg hesperidin or naringin was daily given for 4 weeks after diabetes induction. At the end of the experimental period, blood was obtained from jugular vein and livers were rapidly excised and homogenized for biochemical assays. In the diabetic control group, levels of glucose, glycosylated hemoglobin (HbA1c%), MDA, NO, TNF-α and IL-6 were significantly increased, while serum insulin, GSH, vitamin C, and vitamin E levels were decreased. Both hesperidin and naringin administration significantly reversed these alterations. Moreover, supplementation with either compound significantly ameliorated serum and liver MDA, NO and glutathione, and liver antioxidant enzymes. Although detailed studies are required for the evaluation of the exact mechanism of the ameliorative effects of hesperidin and naringin against diabetic complications, these preliminary experimental findings demonstrate that both hesperidin and naringin exhibit antidiabetic effects in a rat model of T2DM by potentiating the antioxidant defense system and suppressing proinflammatory cytokine production.