Fresh seeds of Piper nigrum were procured from the botanical garden of Kokan Krushi Vidyapeeth, Dapoli, Ratnagiri. The ethanolic extract of the seeds was carried out by soxhlate extraction method. Sixty four (64) Sprague- Dawley rats (average weight 150 - 240 g) of either sex were used for the experiment. The ETH and PAS drugs and Piper nigrum were given to respective groups daily for 28 days. At the end of study various biochemical parameters were analyzed from serum such as of Serum Albumin, Urea, Creatinine, Total proteins and Blood Urea Nitrogen (BUN). The kidney tissues were analyzed for Histopathology. Graph Pad Prism 7 was used for statistical analysis by one way variance (ANOVA). The value p< 0.05 considered as significant. Ethanolic seed extract of Piper nigrum (Linn.) was administered independently as well as in combination with ETH and PAS drugs. It is found that the pretreated test groups with Piper nigrum ameliorated the toxic effect of the drugs. Piper nigrum (.Linn) also showed the normalization of histoarchitecture of the kidney by confirming nephroprotective activity against ETH and PAS drugs. Based on the above results it is concluded that the Piper nigrum act as nephroprotective agent and a good bio-enhancer against nephrotoxicity induced by ETH and PAS drugs in Sprague-Dawley rats.