To study the effect of type A botulinum toxin combined with medical collagen filling agent and sculptra in periocular rejuvenation. Methods From June 2022 to June 2023, 156 patients who underwent periocular rejuvenation treatment in our hospital were selected as the research objects. They were divided into control group (79 patients) and observation group (77 patients) by random number table method. The control group was treated with type A botulinum toxin, and the observation group was treated with botulinum toxin combined with medical collagen filler and sculptra. The wrinkle removal effect, comprehensive effect, periocular score and satisfaction were compared between the two groups. Results The effective rate and comprehensive effective rate of wrinkle removal in the observation group were higher than those in the control group (P<0.05). After treatment, the scores of skin color, fishtail lines and eye bag in the observation group were higher than those in the control group (P<0.05). The satisfaction rate of the observation group was 97.40%, which was higher than 83.54% of the control group (P <0.05). Conclusion Compared with simple type A botulinum toxin treatment, type A botulinum toxin combined with medical collagen filling agent and sculptra can better solve the periocular problems, with better wrinkle removal effect and comprehensive effect, less damage, quick effect and short recovery time, which is conducive to the realization of periocular rejuvenation and the improvement of patient satisfaction