Objective To analyze the efficacy and safety of collagen combined with sodium hyaluronate for injection in the treatment of facial wrinkles. Methods A total of 200 patients with facial wrinkles admitted to Shanghai Baisi Ai Medical Beauty Clinic from June 2023 to April 2024 were selected as the research subjects, and they were divided into the control group and the combined group by the random number table method, with 100 patients in each group. The control group was treated with sodium hyaluronate for injection, and the combined group was treated with collagen on the basis of the control group. The texture and pigment spot scores, adverse reactions and treatment satisfaction were compared between the two groups. Results The scores of texture and pigment spot at 3 months after treatment in the two groups were lower than before treatment, and those in the combined group were lower than those in the control group (P <0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P >0.05). The treatment satisfaction in the combined group was 99.00%, which was higher than 89.00% in the control group (P <0.05). Conclusion The application of collagen combined with sodium hyaluronate for injection in the treatment of facial wrinkles can improve the clinical symptoms of patients, without increasing the incidence of adverse reactions, and can also improve the treatment satisfaction of patients.