This study was designed to investigate the protective effects of sitagliptin on renal damage induced by renal ischemia reperfusion (I/R) in rats. For this, rats were randomly divided into four groups (n = 8): (1) sham group, in which the rats only underwent right nephrectomy; (2) right nephrectomy and left kidney ischemia (1 h) and reperfusion (24 h) group (I/R); (3) 5 mg/kg sitagliptin administrated group, per-oral once a day for two weeks; (4) 5 mg/kg sitagliptin administrated group, per-oral once a day for two weeks before left kidney I/R (n = 8). Sitagliptin-treated rats that underwent renal I/R demonstrated significant decrease in the serum urea nitrogen and creatinine and also, lipid peroxidation, total oxidant status and malondialdehyde level in the renal tissue when compared to the renal I/R group. Additionally, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase and total antioxidative capacity were significantly increased after renal I/R in sitagliptin-treated rats. Our histopathological findings were in accordance with these biochemical results. In sum, in the current study all of our results indicated that sitagliptin treatment ameliorated renal damage induced by renal I/R in rats.