This study investigates the in vitro antioxidant potentials and attenuation of acetaminophen-induced redox imbalance by Pterocarpus osun Craib (Fabaceae) leaf in Wistar rat liver. The in vitro antioxidant activity of the extract (0.2-1.0 mg/mL) was evaluated using 2,2-diphenyl-1-picrylhydrazl (DPPH), hydrogen peroxide, superoxide ion, 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate (ABTS), and ferric ion. The extract (150 and 300 mg/kg body weight) significantly (P<0.05) attenuated the altered liver and serum enzymes of acetaminophen treated animals. Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities as well as vitamins C and E, and glutathione levels were significantly (P<0.05) elevated by the extract. The activities of uridyl diphosphoglucuronosyl transferase (59%), quinone oxidoreductase (53%), and glutathione S-transferase (73%) significantly increased. The extract of P. osun leaf extract at 1.0mg/mL scavenged the DPPH, hydrogen peroxide, superoxide ion, and ABTS at 94, 98, 92, and 86%, respectively, while ferric ion was significantly reduced. There was attenuation of malondialdehyde and lipid hydroperoxide. The results indicates that P. osun leaves attenuated acetaminophen-induced redox imbalance, possibly acting as free radical scavenger, inducer of antioxidant and drug-detoxifying enzymes, which prevented/reduced lipid peroxidation.