Objective To explore the efficacy and safety of glycolic acid combined with microneedle-introduced recombinant mussel adhesive protein wound dressing in the treatment of post-inflammatory hyperpigmentation (PIH). Methods A total of 60 patients with PIH admitted to the Department of Dermatology, Luliang County First People's Hospital from January 2023 to December 2024 were selected, and they were divided into the control group and the observation group by the random number table method, with 30 patients in each group. The control group was treated with glycolic acid combined with microneedle-introduced recombinant collagen solution, and the observation group was treated with glycolic acid combined with microneedle-introduced recombinant mussel adhesive protein wound dressing. The overall skin quality improvement, VISIA skin image indicators, skin barrier function and adverse reactions were compared between the two groups. Results At 2 and 4 weeks after treatment, the GAIS scores of the observation group were higher than those of the control group (P <0.05). The VISIA scores of spots, ultraviolet spots, brown spots and red areas in the observation group after treatment were lower than those in the control group (P <0.05). The stratum corneum hydration and TEWL of the observation group after treatment were better than those of the control group (P <0.05). The incidence of adverse reactions in the observation group was 3.33%, compared with 6.67% in the control group, the difference was not statistically significant (P >0.05). Conclusion Glycolic acid combined with microneedle-introduced recombinant mussel adhesive protein can effectively improve PIH, lighten various pigment subtypes and associated erythema, and effectively repair skin barrier function, with good safety. It is worthy of clinical application.