Objective To analyze the efficacy and safety of collagen combined with type A botulinum toxin in periorbital rejuvenation treatment. Methods A total of 60 patients who underwent periorbital rejuvenation treatment in Changsha Arsnmo Plastic & Aesthetic Hospital from August 2022 to September 2024 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 30 patients in each group. The control group was treated with type A botulinum toxin, and the observation group was treated with collagen combined with type A botulinum toxin. The treatment effect, adverse reactions, skin condition, skin barrier function and facial aesthetics were compared between the two groups. Results The total effective rate of treatment in the observation group (96.67%) was higher than that in the control group (80.00%) (P <0.05). The incidence of adverse reactions in the observation group (0) was lower than that in the control group (13.33%) (P <0.05). After treatment, the skin moisture level and elasticity level in the observation group were higher than those in the control group (P <0.05). After treatment, the sebum content and stratum corneum hydration in the observation group were higher than those in the control group, and the TEWL and pH value in the observation group were lower than those in the control group (P <0.05). After treatment, the aesthetics score in the observation group was higher than that in the control group (P <0.05). Conclusion The application of collagen combined with type A botulinum toxin in periorbital rejuvenation treatment has a good effect. It can effectively improve the skin condition and facial aesthetics of patients, and help to enhance their skin barrier function. Meanwhile, the incidence of adverse reactions after treatment is low, and the efficacy and safety of application are high.