ETHNOPHARMACOLOGICAL RELEVANCE: Persea americana Miller (Lauraceae) known as "pear" in Cameroon is comestible by the fruit. The leaves of the plant are traditionally used in the treatment of microbial infections, malaria, diabetes, high blood pressure, to stimulate uterine contractions and relief painful menstruations. The leaves and stem bark are also used to cure malaria and typhoid fever. Fresh pulps are used to lower cholesterol, prevents mental strain and cardiovascular diseases whilst the seeds are used against intestinal worms and skin infections. AIM OF THE STUDY: This study aimed to investigate the antibacterial activity and wound healing efficacy of methanol extract of Persea americana seed on an excision wound infected with Staphylococcus aureus using a rat model and characterise the mode of action of this extract. MATERIALS AND METHODS: The antibacterial activities of the methanol extract were done against a panel of bacteria using broth microdilution method. The phytochemical analysis as well as the antioxidant activities were evaluated using colorimetric methods. The mode of action of P. americana was studied by targeting bacterial membranes, cytoplasmic contents, and the formation of biofilms. The therapeutic effect of the methanol extract was evaluated on an excision wound infected with Staphylococcus aureus. RESULTS: The methanol extract of P. americana seed displayed antibacterial properties MIC varying from 64 to 128 µg/mL which can be linked to its total phenolic, flavonoid and tannin contents. The antibacterial activity of the extract is due to the bacterial biofilm inhibition and the perturbation of the bacterial membrane through the leakage of intracellular materials, the inhibition of H+-ATPases pumps. The gel based on P. americana extract showed a significant increase in the percentage of wound closure and had a significant reduction of the number of Colony Forming Units (CFU) of S. aureus at the infection site. The plant has antioxidant activity for wound healing which is lower than vitamin C. The toxicological report showed that the gel-based extract had negligible irritation on the skin and non-irritating to the eye, and therefore can be consider safe for use. CONCLUSION: The present study revealed the antibacterial and wound healing properties of the MEPa and could possibly be used to tackle bacterial infections.