Diabetic nephropathy is a serious complication for diabetic patients, yet the precise mechanism that underlies the development of diabetic complications remains unknown. We hypothesised that dietary antioxidant supplementation with single N-acetylcysteine (NAC) or vitamin C combined with either vitamin E or vitamin E and NAC improves diabetic renal inflammation through the modulation of blood glucose levels, oxidative stress and inflammatory response. Experimental animals were treated with alloxan monohydrate to induce diabetes. Mice were divided into five groups and supplemented with single or a combination of antioxidants. Body weights and blood glucose levels were measured once a week. After 8 weeks of dietary antioxidant supplementation, mice were killed and blood urea N (BUN) and plasma creatinine levels were measured to evaluate renal function. NF-κB protein was indirectly demonstrated by the phosphorylated IκBα (pIκBα) level, and the expressions of oxidative stress- and inflammatory response-related proteins were also determined. We demonstrated that dietary antioxidant supplementation decreased lipid peroxidation levels demonstrated by thiobarbituric acid-reacting substances, BUN and plasma creatinine levels in diabetic kidneys. Moreover, dietary antioxidant cocktail supplementation improved blood glucose levels and selectively regulated the expressions of Cu-Zn superoxide dismutase, haeme oxygenase-1, pIκBα, inducible NO synthase, cyclo-oxygenase-2 and C-reactive protein in diabetic kidneys effectively. These findings demonstrated that diabetic renal failure was associated with inflammatory responses induced by hyperglycaemia. In addition, results in the study suggest that antioxidant cocktail supplementation may have beneficial effects on diabetic nephropathy through selective reduction of blood glucose levels and inflammatory response.