Acetaminophen (APAP) is a commonly used analgesic and antipyretic agent which, in high doses, causes liver and kidney necrosis in man and animals. Herbal medicines have recently attracted much attention as alternative medicines for treating or preventing life style related disorders of nephrotoxicity but relatively very little knowledge is available about their mode of action. Anthoxanthum odoratum Linn (Sweet Vernal Grass), family “Poaceae” is especially provocative to hay fever and hay asthma, a medicinal tincture from it is sniffed well into the nose and throat for immediate relief from congestion. It has been reported to be biologically active for growth inhibitor and effective for nephrotoxic activity.The aim of the present study was to investigate the nephrotoxic and antioxidant activities of the ethanol extract of Anthoxanthum odoratum at two doses level of 250mg/kg & 500 mg/kg B/W on acetaminophen- induced toxicity in rats. Biochemical studies shows that increased the levels of body weight, serum urea, hemoglobin (Hb), total leucocyte count (TLC), creatinine (CR), packed cell volume (PCV), differential leucocyte count (DLC) and mean corpuscular volume (MCV) along with reduction in the levels of neutrophil, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), granulocytes, uric acid, platelet concentration (PLC) in acetaminophen- induced groups. These values are retrieved significantly with treatment of Anthoxanthum odoratum extract at two different doses. The antioxidant study reveals that the levels of renal superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione peroxidase (GPx) in the APAP treated animals are increased significantly along with decreased malonodialdehyde (MDA) content in ethanol extract of Anthoxanthum odoratum treated groups. In conclusion, these data suggest that the ethanol extract of Anthoxanthum odoratum can prevent renal damage from APAP-induced nephro toxicity in rats and this is likely mediated through its antioxidant activities.