Abstract: The present study investigated antioxidant activities of Leonotis leonurus extract both in vivo and in vitro to provide scientific basis to traditional usage of this plant. The in vitro antioxidants activity was evaluated by determining ferric reducing power, total flavonoids, phenolics, flavonols and proanthocyanidins contents using standard assay methods. The ability of the extract to scavenge 2, 2 diphenyl-2-picrylhydrazyl (DPPH), Nitric Oxide (NO), 2, 2-azinobis [3-ethylbenzothiazoline-6-sulfonic acid] diammonium salt were also assessed using spectroscopic method. Oral administration of L. leonurus extract at the doses of 125, 250 and 500 mg kg-1 body weight was evaluated in Wistar rats induced with carbon tetrachloride (CCl4) for 7 days. The extract effectively increased the percentage inhibition of reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). However, lipid peroxidation was significantly decreased in CCl4 treated rats with the extract when compared with the diabetic control rats. The plant extract (0.8 mg mL-1) scavenge DPPH.+ ABTS.+ and NO.+ by inhibiting 72.48, 78.02 and 70.43% of the radicals, respectively. The reducing power of the extract was found to be concentration dependent. In addition, the extracts yielded higher phenolics content followed by flavonoids, proanthocyanidins and flavonols. A positive linear correlation was established between these polyphenols and the free radical scavenging activities. The results obtained from this study indicate that L. leonurus is a potential source of antioxidants and thus could prevent many radical related diseases.