Oxidative stress has been suggested to be a contributory factor in the development and complication of diabetes. Clinical research has confirmed the efficacy of several phytochemicals in the modulation of oxidative stress associated with diabetes mellitus. Oral administration of the combination of tetrahydrocurcumin (THC) at 60 mg/kg body weight and gallic acid (GA) at 15 mg/kg body weight to diabetic rats for 45 days resulted in significant reduction in blood glucose and leptin, and significant increase in plasma insulin, and quantitative insulin sensitivity check index (QUICKI) levels. In addition, combination of THC and GA caused significant increase in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, reduced glutathione, vitamin C and vitamin E in the liver and kidney of diabetic rats with a significant decrease in thiobarbituric acid reactive substances (TBARS) and hydroperoxides formation in liver and kidney, suggesting its role in the protection against lipid peroxidation-induced membrane damage. The histopathological examination of liver and kidney also confirmed these biological observations. The present study indicates that the combination of THC and GA exerts a significant beneficial effect on antioxidant defense in addition to its antidiabetic effect. The combination effect of THC and GA was better when compared with that of THC or GA alone.