Since kidneys are the vital excretory organs carrying diverse functions, effective and safer drug treatments are required to treat renal disorders. Oxidative renal stress due to generation of reactive oxygen species is the reason for gentamycin induced nephrotoxicity. Our work was researched to evaluate the nephroprotective and antioxidant activity of ethanolic leaf extracts of momordica dioica. Group I control group received distilled water. Gentamycin(80 mg/kg, ip) was injected to group II rats once daily for 8 days (negative control). Cystone drug induced rats were used as positive control (group III). Group IV and V rats were orally pretreated for 6 weeks with ethanolic leaf extracts of plant along with gentamycin induction during the last 8 days. After the experimental period serum renal biomarkers levels and renal antioxidant enzymes levels were estimated. Gentamycin treated rats showed after 8 days reduced activity of renal antioxidant enzymes and increased levels of serum biomarkers. Orally pre-treated rats for 6 weeks with plant extracts, after experimental period produced significant nephroprotective and antioxidant activity in gentamycin induced nephrotoxic rats by reversing all these parameters levels. Nephroprotective and antioxidant activity of ethanolic leaf extracts of Momordica dioica have been proved.