Objective To observe the application effect of active collagen filler combined with polylactic acid in perioral rejuvenation treatment. Methods A total of 71 patients who received perioral rejuvenation treatment in Liuzhou Huamei Medical Cosmetology Clinic from April 2022 to April 2024 were selected as the research subjects. According to the random number table method, they were divided into the control group (35 patients) and the combination group (36 patients). The control group was given polylactic acid alone, and the combination group was given active collagen filler on the basis of the control group. The wrinkle severity, clinical efficacy and adverse reactions were compared between the two groups. Results The WSRS score of the two groups after 4 months of treatment was lower than that before treatment, and that of the combination group was lower than that of the control group, and the difference was statistically significant (P <0.05). The total effective rate of treatment in the combination group (97.22%) was higher than that in the control group (80.00%), and the difference was statistically significant (P <0.05). The incidence of adverse reactions in the combination group (2.78%) was lower than that in the control group (17.14%), and the difference was statistically significant (P <0.05). Conclusion The application of active collagen filler combined with polylactic acid in perioral rejuvenation treatment can effectively improve clinical symptoms, enhance treatment effect, and reduce the incidence of adverse reactions.