The effect of ethanol extract of Phyllanthus maderaspatensis (PME), a popular south Indian dietary supplement, was studied for its chemoprotective property on adriamycin (ADR)-induced toxicity and oxidative stress in mice. Adriamycin toxicity was evaluated biochemically by measuring the serum concentration of lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK). Genotoxicity was evaluated by measuring the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow cells. Oxidative stress in the heart tissue was estimated by measuring the glutathione (GSH) levels in the homogenate. The treatment of mice with different doses of PME (400 mg/kg and 600 mg/kg body weight, p.o.,) for 7 days before the administration of a single i.p. dose of ADR (15 mg/kg) exhibited significant protection in a dose-dependent manner. The results clearly indicate that PME has a protective effect against ADR-induced toxicity, as revealed by the decrease in the concentrations of LDH, CPK, and the frequency of MNPCEs. The increased levels of GSH are indicative of the antioxidant property of PME.