To investigate the effect of collagen combined with polydioxanone (PPDO) protein line on periorbital rejuvenation. Methods The clinical data of 149 beauty seekers admitted to our hospital from July 2021 to July 2022 were retrospectively analyzed. According to different treatment methods, they were divided into observation group (75 beauty seekers) and control group (74 beauty seekers). The control group was treated with PPDO protein line implantation, and the observation group was treated with collagen combined with PPDO protein line. The clinical efficacy, tear trough and periorbital skin improvement, quality of life and complications were compared between the two groups. Results The total effective rate of treatment in the obs ervation group was 94.67%, which was higher than 81.08% of the control group (P <0.05). After treatment, the scores of lacrimal groove, zygomatic fat pad prolapse, pigmentation and skin folds in the observation group were lower than those in the control group (P <0.05). After treatment, the scores of skin relaxation, double eyelid width and fishtail lines improvement in the observation group were higher than those in the control group (P <0.05). After treatment, the scores of physical function, psychological function, material life and social function in the observation group were higher than those in the control group (P <0.05). There was no significant difference in the incidence of complications between the observation group and the control group after treatment (P >0.05 ). Conclusion Collagen combined with PPDO protein line is effective in the treatment of periorbital rejuvenation, which can effectively improve the periorbital skin state of patients, improve their quality of life, and is safe and reliable.