To evaluate nephroprotective potential of Solanum xanthocarpum (S. xanthocarpum) fruit extract(SXE) against gentamicin (GM) induced nephrotoxicity and renal dysfunction. Twenty-four Wistar rats were divided into four groups (n=6). Control rats that received normal saline (i.p.) and 0.5% carboxymethyl cellulose (p.o.) per day for 8 d. Nephrotoxicity was induced in rats by intraperitoneal administration of GM (100 mg/kg/d for 8 d) and were treated with SXE (200 and 400 mg/kg/d (p.o.) for 8 d). Plasma and urine urea and creatinine, kidney weight, urine output, blood urea nitrogen, renal enzymatic and non-enzymatic antioxidants and lipid peroxidation was evaluated along with histopathological investigation in various experimental groupsof rats. It was observed that the GM treatment induced significant elevation (P<0.001) in plasma and urine urea, creatinine, kidney weight, blood urea nitrogen, renal lipid peroxidation along with significant decrement (P<0.001) in urine output, renal enzymatic and non-enzymatic antioxidants. SXE 200 and 400 mg/kg treatment to GM treated rats recorded significant decrement (up to P<0.001) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (up to P<0.001) in renal enzymatic and non-enzymatic antioxidants. Histological observations of kidney tissues too correlated with the biochemical observations. These finding powerfully supports that S. xanthocarpum fruit extract acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GM both in the biochemical and histopathological parameters and thus validates its ethnomedicinal use.