Since decades ago, humans have been using natural products such as plants in medicines. Currently, traditional medicine has become popular. Plants contain numerous phytochemicals that may act synergistically through different mechanisms for prophylaxis and therapy of diseases. This study evaluated the anti-oxidative and wound healing activities of Chromolaena odorata methanol leaf extract using mature male rat models. Phytochemical analysis, acute toxicity study, anti-oxidative potentials as well as wound healing activities of the leaf extract were assessed. In anti-oxidative study, the effects of Chromolaena odorata methanol leaf extract on malondialdehyde (MDA) and catalase were tested. In the wound healing, excision wounds were created on the back of the rats and the wounds were treated with three different doses of Chromolaena odorata methanol leaf extract embedded in petroleum jelly. Cikatrin powder and petroleum jelly served as positive and negative controls respectively. The phytochemicals present were alkaloids, flavonoids, proteins, tannins, and steroids. LD50 ˃ 5,000 mg/kg body weight was noted. In anti-oxidative assay, the leaf extract had better lipid peroxidation inhibition. The 500 mg/kg body weight of the extract reduced MDA to 5.63 ± 0.33 x 10-5 µmol/ml compared to 14.16 ± 0.59 x 10-5 µmol/ml obtained with distilled water. The 5% and 10% extracts had better percentage wound healing of 95.52% and 97.14 % respectively than cikatrin which had 87.95% after 12 weeks of treatment. Chromolaena odorata methanol leaf extract had good safety profile and a dose dependent increase in wound healing that is significantly (p ˂ 0.05) more potent than cikatrin.