Methotrexate (MTX) is one of the most broadly used anti-cancer derivative of aminopterin and it is a first folic acid antagonist. Adult cancer, various malignancies, multiple sclerosis, dermatomyositis, sarcoidosis, psoriasis, rheumatoid arthritis, and severe inflammatory disorders are all commonly treated with MTX. Medicinal plants and herbs contribute, wide range of treatment and prevention from several diseases. Herbal formulations mean dosage form consisting of one or more plants prepared herbs in selected quantities to cure mitigate diseases, by treatment, prevention and sometimes use as a supplement. Petrida foetida is used as traditionally diarrhea, stomach ache and nutritional supplement etc. Vitis vinifera, the fruit is used for dietary and the leaves and seeds are used as several herbal therapy. The current study had carried out to evaluate the nephroprotective activity of leaves and seed extracts of Petrida foetida and Vetis venifera. Nephroprotective activities of ethanolic and aqueous extracts of Petrida foetida and Vitis vinifera seeds were examined against methotrexate induced Kidney damage in Sprague Dawley Rats. Biochemical parameter evaluates like Urea, Creatinine, Uric acid, Blood urea nitrogen, total protein like albumin, globulin was analyzed. Petrida foetida and Vitis venifera seeds extract of exhibited significant (p<0.05) nephroprotective activity. Ethanolic seeds extract of Vitis vinifera and Petrida foetida menifest moderate activity upon Methotrexate induced Rat models. Study outcome shows the traditional-ethno medicinal use of Methotrexate as a potential source of Nephroprotective activity.