This study was aimed to investigate the antioxidant potentials of methanol and petroleum ether leaf extracts of Asystasia vogeliana against paracetamol-induced liver injury in rats. For estimation of antioxidant potentials, in vitro radical scavenging assays were carried out using DPPH, FRAP, and ABTS. For in vivo study, twenty-five male Wistar rats weighing 100-120 g were randomized and assigned into 5 groups (I-V, n=5). Further, Paracetamol (PCM) at 2 g/kg was used to induce acute hepatotoxicity orally. Rats in group I received distilled water (10 ml/kg) only. While, the rats of groups II, III, and IV received MLEAV (200 mg/kg), PLEAV (200 mg/kg), and a standard hepatoprotective reference drug silymarin (25 mg/kg) respectively for 5 days before PCM induction. Rats in group V received distilled water for 5 days before PCM induction. Blood and liver samples were collected for hematology, serum biochemistry, and histopathology analyses using standard procedures. In vitro assays revealed that MLEAV showed significant (P < 0.05) increases in antioxidant activity compared with PLEAV. Further, significant (P < 0.05) reductions in the activities of ALT and ALP while a significant (P < 0.05) increases in the activity of antioxidant enzymes (CAT, SOD, and GPx) were reported in the group II and III compared with group V. There were also no observable lesions in their hepatocytes. Results of the study can be concluded that MLEAV elicited more in vitro and in vivo antioxidant activities than PLEAV, thus it protects the liver of rat from PCM-induced hepatotoxicity. Therefore, MLEAV could be used as a hepatoprotective agent for the clinical management of liver damage.