Wound healing is a well-coordinated process that restores skin integrity upon injury. However, some wound treatment poses harmful effects on the skin, which delay the normal wound healing process. Marphysa moribidii, a marine baitworm or polychaete, represents unique ability to regenerate posterior segment after injury, which may be beneficial in the wound healing treatment. The effectiveness of the polychaete as wound healing treatment was discovered through skin irritation, microbial testing, animal wound model, and chemical identifications. Three polychaete extracts (PE) emulsifying ointment (0.1%, 0.5%, and 1.0%) were topically applied to the full thickness wound model once daily for 14 days. Interestingly, PE 1.0% revealed the most rapid wound healing effects as compared to other treatments, including gamat (sea cucumber) oil (15% w/v) and acriflavine (0.1% w/v). Histopathological analysis using Masson's trichrome staining further confirms that PE treated wound exhibited minimal scar, high collagen deposition, and the emergence of neovascularisation. The extract also displayed a minimum inhibitory concentration (MIC) of 0.4 g/ml against Escherichia coli and absence of skin irritation, infectious bacteria, and heavy metals from the extract. Moreover, chemical compounds such as alkaloid, flavonoid, amino acids, and organic acid were detected in M. moribidii extracts, which could contribute to wound healing activity. In conclusion, this study further justifies the beneficial use of polychaete in treating wound healing and could be developed as a novel bioactive agent in nutraceuticals and pharmaceutical drugs.