N-nitrosodimethylamine (NDMA) is an important carcinogen frequently present in human environment and food chain. Nitrosamines such as NDMA produce oxidative stress due to generation of reactive oxygen species and alter the antioxidant defense system in the tissues. Chronic kidney disease due to a number of factors is a common and serious problem that adversely affects human health, limits longevity and increases costs to health-care systems worldwide. Oxidative stress is prevalent in kidney diseases and is considered to be an important causative mechanism. It develops from an imbalance between free radical production often increased through dysfunctional mitochondria formed with increasing age, inflammation, and reduced anti-oxidant defenses. The present study investigates the influence of ethanolic extract of Operculina turpethum roots on the kidney of NDMA intoxicated mice. The nephrotoxicity and therapeutic effect of the plant was assessed by the analysis of kidney marker enzymes, antioxidant enzymes and kidney histopathological studies. NDMA exposure produced detrimental effects on the redox status of the kidney indicated by a significant decline in the levels of protein and antioxidants such as superoxide dismutase, catalase, and glutathione and increased cholesterol, AST, ALT, ALP and lipid peroxidation. Operculina turpethum manifested chemopreventive effects by significantly restoring the enzymatic levels and reducing the nephrotoxicity in mice. Histological examination of kidney revealed patho-physiological changes in NDMA treated mice and improved plant treated renal histopathology.