Discopodium Penninervum Hochst is among the Ethiopian medicinal plants traditionally used for wound healing activity. However, to date, there is no scientific report on its wound healing activity. Thus, the main aim of this study was to investigate the wound healing activity of 80% methanol leaf extract of D. penninervum in mice. Wound healing activity was investigated using excision and incision wound models. Mice were randomly assigned and treated with simple ointment (negative control), nitrofurazone (positive control), 5%, and 10% of D. Penninervum extract. Parameters such as wound contraction, period of epithelialization and tensile strength were evaluated. In addition, anti-inflammatory test using carrageenan-induced hind paw oedema model, in vitro antibacterial activity using agar well diffusion technique against several common bacterial strains that cause wound infection and antioxidant activity studies were performed at different doses of the extract. Both 5% and 10% (w/w) ointments exhibited significant ( p < 0.001) increase in wound contraction and shorter epithelization period in excision wound model. Animals treated with 5% and 10% (w/w) ointments showed about 97% and 98% wound closure, respectively, on day fifteen, while the closure of negative control was 88%. In addition, both preparations of the crude extract showed significant increase ( p < 0.001) in wound tensile strength as compared to negative controls. Mice treated with 100 mg/kg, 200 mg/kg and 400 mg/kg extract showed significant ( p < 0.001) reduction in paw oedema starting from the 2 nd h as compared to negative controls with maximum inhibition of 56.27%, 57.36% and 58.18%, respectively. The crude extract also showed antibacterial activity against both Gram- positive and Gram-negative bacteria, with the former being more sensitive than the latter. The lowest MIC values were observed for S. aureus , (2.6 µg/µl) and the highest (350 µg/µl) for all the studied Gram-negative organisms. The MIC index of the extract was found to be 2. The extract was effective in scavenging DPPH radicals and its IC 50 value was 2.77 mg/ml. In addition, quantification of total flavonoid content revealed the presence of 43.03 mg quercetin equivalent flavonoids in the extract. In conclusion, the extract of D. penninervum is endowed with significant wound healing activity that could be attributed to antibacterial, anti-inflammatory and antioxidant activities of the plant. Keywords: Discopodium penninervum , wound healing, excision and incision models, antibacterial activity, anti-oxidant activity