Adhatoda vasica Nees (Acanthaceae) that is used by Ayurvedic physicians possesses some established medicinal properties. Environmental and occupational exposure with cadmium affects the renal system adversely. Cadmium is an established genotoxic agent. In the present study, we evaluated the antioxidant and anticlastogenic efficacy of A. vasica against cadmium chloride (CdCl2)-induced renal oxidative stress and genotoxicity in Swiss albino mice. A single intraperitoneal dose of CdCl2 (5 mg\kg BW) resulted in significant (p<0.001) increase in chromosomal aberration and micronuclei formation. Oral administration of A. vasica at two doses (50 and 100 mg/kg BW) for seven consecutive days showed significant (p<0.001) suppression of mutagenic effects of CdCl2 in plant-pretreated groups. To study the mechanism by which A. vasica exerts its antimutagenic potential, enzymes involved in metabolism and detoxification were also estimated. Cadmium intoxication altered the antioxidant levels and enhanced MDA formation significantly (p<0.001). A. vasica showed significant (p<0.001) recovery in antioxidant status, viz., GSH content, its dependent enzymes, and catalase activity. Prophylactic pretreatment of A. vasica extract in cadmium-intoxicated mice showed marked (p<0.001) inhibition of lipid peroxidation (LPO) and xanthine oxidase (XO) activity. The present findings support that antimutagenic efficacy of A. vasica can be attributed to its restoring effects on antioxidant status and suppression of MDA level formation.