This study aimed to evaluate the effects of aqueous and methanolic extracts of Commelina diffusa on gentamicin induced-nephrotoxicity in rats. Nephrotoxicity was induced by intraperitoneal injection of gentamicin (80 mg/kg) for 10 days. Simultaneous, extracts were administered at doses of 100 and 200 mg/kg. Silimaryn (100 mg/kg) was used as reference drug. At the end of the experimental period, body weight, kidney weight, urine output, biochemical and antioxidants parameters were evaluated; kidney tissues were also examined. Results showed that gentamicin induced nephrotoxicity confirmed by a significant (p <0.05 to p <0.001) increased in serum urea, sodium and creatinine levels, and a significant (P<0.05) decreased of urine creatinine level in negative control group. In the same group, the activities of superoxide dismutase and catalase, and the levels of gluthation and serum protein were significantly decreased while malondialdehyde level was increased compared to normal control. Aqueous and methanolic extracts of C. diffusa significantly reversed all the altered parameters. Histopathological examination of kidney tissues revealed that aqueous extract of C. diffusa at dose of 200 mg/kg repaired the renal damage induced by gentamicin. In conclusion, aqueous and methanolic extracts of C. diffusa possess nephroprotective effects.