Objective To explore the efficacy of recombinant mussel adhesive protein (rMAP) in wound repair after CO2 fractional laser surgery in patients with depressed acne scars. Methods A total of 70 patients with depressed acne scars treated in Kunming Dermatology Specialized Hospital from March 2025 to March 2026 were selected, and they were divided into the control group and the observation group by the random number table method, with 35 patients in each group. Both groups received CO2 fractional laser treatment. The control group was treated with medical collagen immediately after laser surgery, and the observation group was treated with rMAP immediately after laser surgery. The wound healing duration, inflammatory response, skin barrier function, VISIA examination results, subjective sensation, overall satisfaction and adverse reaction rate were compared between the two groups. Results The wound incrustation time and decrustation time of the observation group were shorter than those of the control group (P <0.05). At 30 min after surgery, the scores of erythema, edema and exudation in the observation group were lower than those in the control group (P <0.05). At 3 and 28 days after surgery, the TEWL in the observation group was lower than that in the control group, and the stratum corneum hydration was higher than that in the control group (P <0.05). The proportion of red area in the observation group at 30 min and at 3 and 28 days after surgery was lower than that in the control group (P <0.05). At 3 and 28 days after surgery, the melanin value in the observation group was lower than that in the control group (P <0.05). At 28 days after surgery, the scores of facial dryness, tightness and pruritus in the observation group were lower than those in the control group (P <0.05). The overall satisfaction rate of the observation group was 94.29%, which was higher than 77.14% of the control group (P <0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion rMAP exhibits definite efficacy in wound repair after CO2 fractional laser surgery in patients with depressed acne scars. It can shorten the wound healing duration, alleviate postoperative inflammatory response, reduce melanin value and the proportion of red area, help to promote the recovery of skin barrier function, and improve patients' subjective sensation, without increasing the risk of adverse reactions. The application safety is good, and the overall satisfaction of patients is high.