Objective To analyze the effect of poly-L-lactic acid layered injection in pan-perioral injection treatment. Methods A total of 130 patients who underwent pan-perioral treatment in Liudalie (Guangzhou) Medical Cosmetology Clinic from February 2022 to April 2023 were selected as the research subjects. According to the random number table method, they were divided into the control group and the observation group, with 65 patients in each group. The control group received sodium hyaluronate gel injection treatment, and the observation group received poly-L-lactic acid layered injection treatment. The pan-perioral skin condition, nasolabial fold score, marionette line score, facial relaxation score, clinical efficacy and treatment satisfaction were compared between the two groups. Results At 12 months after treatment, the scores of skin hydration and elasticity in the observation group were higher than those in the control group, and the scores of nasolabial fold, marionette line and facial relaxation were lower than those in the control group (P <0.05). The total effective rate of the observation group was 98.46%, which was higher than 70.77% of the control group (P <0.05). The total treatment satisfaction rate of the observation group was 86.15%, which was higher than 64.62% of the control group (P <0.05). Conclusion Poly-L-lactic acid layered injection treatment has a good clinical effect in pan-perioral rejuvenation, which can effectively improve skin hydration and elasticity, reduce nasolabial folds, marionette lines and facial relaxation, and has high patient satisfaction.