Objective To explore the clinical effect of midfacial lifting combined with blepharoplasty in the treatment of women with periorbital skin wrinkles. Methods A total of 200 patients with periorbital skin wrinkles admitted to our hospital from January to December 2022 were selected as the research objects. They were divided into control group and observation group by random number table method, with 100 patients in each group. The control group was treated with blepharoplasty, and the observation group was treated with blepharoplasty combined with midface lifting. The clinical efficacy, quality of life, wound healing time, hospitalization time, complications and cosmetic satisfaction were compared between the two groups. Results The total effective rate of treatment in the observation group was 95.00%, which was higher than 80.00% in the control group, and the difference was statistically significant ( P <0.05). After treatment, the scores of quality of life in the observation group were better than those in the control group, the differences were statistically significant ( P <0.05). The wound healing time and hospitalization time of the observation group were shorter than those of the control group, and the differences were statistically significant ( P <0.05). The incidence of complications in the observation group was 3.00%, which was lower than 15.00% in the control group, and the difference was statistically significant ( P <0.05). The cosmetic satisfaction of the observation group was 95.00%, which was higher than 80.00% of the control group, and the difference was statistically significant ( P <0.05). Conclusion The application of midface lifting combined with blepharoplasty in women with periorbital skin wrinkles has a definite clinical effect, which can improve the psychological state, improve the quality of life, shorten the hospitalization time and wound healing time, and has high safety. Meanwhile, it can improve patient satisfaction and is worthy of clinical application.