This study was aimed to investigate the therapeutic potential of coenzyme Q10 and its combination with sitagliptin in experimentally induced diabetic nephropathy. The diabetic rats were treated with coenzyme Q10 or sitagliptin and their concomitant administration. Various parameters of renal function like serum creatinine, urea, uric acid and markers of oxidative stress such as renal malondialdehyde content (MDA), glutathione (GSH) level and superoxide dismutase (SOD), catalase activities were measured. TNF-α, TGF-β, MPO activity and nitrite content were estimated in renal tissue with histopathological observation. Diabetic rats showed a significant reduction in renal function, which was reflected with an increase in serum creatinine, urea and uric acid levels. Streptozotocin-nicotinamide caused renal tubular damage with a higher MDA level, depletion of SOD and CAT activity and GSH level. In addition, TNF-α, TGF- β, MPO activity and nitrite content were significantly increased in diabetic rats. Treatment with coenzyme Q10 or sitagliptin and their co-administration ameliorated STZ-nicotinamide-induced renal damage which was reflected by decreased oxidative stress, TNF-α, TGF-β, MPO activity, nitrite content along with histopathological changes. To conclude, concomitant administration of coenzyme Q10 and sitagliptin showed a better renoprotective effect than coenzyme Q10 or sitagliptin when given alone.