Background: Renal disease is a significant issue of global proportions and renal damage is very prevalent as the kidney has the ability to excrete toxic substances to assess the protective impact of the Ethanolic extract of Alternanthera sessilis Linn. (EEAS) plant leaves against gentamicin induced nephrotoxicity in rats. Materials and Methods: Nephroprotective activity was assessed by inflicting gentamicin (80 mg/kg) in all groups; acute kidney dysfunction is proven by the vital increment of blood serum creatinine, uric acid, BUN and decline in the total protein, albumin, and globulin with various histological damages. Results: Treatment with the Alternanthera sessilis has appeared critical dosage subordinate change at the measurements of 100 and 200mg/kg by securing the kidney from oxidative stretch. It is additionally recognized that treatment with Alternanthera sessilis essentially brought down the level of serum creatinine, uric acid, BUN and increment within the add up to protein, egg whites, globulin when compared to illness gather. Nephroprotective action of EEAS was found when compared with the standard bunch (Vitamin E 250 mg/kg) and control bunch against the infection gather creatures in parameters counting creatinine, urea, uric corrosive, Blood Urea Nitrogen (BUN), add up to protein, egg whites and globulin. The histopathological considers were moreover proving the defensive impact of EEAS. Conclusion: From the above results it was concluded that the ethanolic extract of Alternanthera sessilis offers nephroprotection.