Objective: To evaluate the potential nephroprotective and antioxidant activity of hydroalcoholic Cissampelos pareira (C. pareira) whole plant extract using gentamicin-induced rats. Methods: For studying acute toxicity study, single oral dose of 2g/kg hydroalcoholic extract of C. pareira was evaluated in rats by oral gavage. The nephroprotective activity was evaluated using gentamicin-induced model in rats. In-vitro antioxidant activity was evaluated by using DPPH assay and reducing power assay. In-vivo antioxidant activity was evaluated by using glutathione and lipid peroxidation estimations in gentamicin-induced rats. Hydroalcoholic C. pareira whole plant extract was given at a dose of 200 and 400 mg/kg p.o. Results: For acute toxicity testing rats administered with the extract at a dose 2 g/ kg. the result showed no toxicity. Hydroalcoholic C. Pareira whole plant extract (200 and 400 mg/kg p.o) significantly decrease the elevated urinary glucose levels in the urine, decrease the elevated urea and creatinine levels in blood and increase the urinary creatinine levels in gentamicin-induced nephrotoxic rats. The extract had shown significant dose dependent increase in the DPPH and reducing power activity. There were a dose dependent decreasing and increasing of lipid peroxidation, glutathione levels in hydoalcoholic extract treated groups respectively. Conclusion: This study exhibits that hydroalcoholic C. pareira whole plant extract poses nephroprotective activity which may be due to its antioxidant activity.