Objective To analyze the application value of supramolecular salicylic acid chemical peeling agent in the treatment of mild to moderate acne and its impact on patients' skin barrier function. Methods A total of 86 patients with mild to moderate acne admitted to Zunyi Maternal and Child Health Hospital from November 2022 to January 2024 were selected as the research subjects, and they were divided into control group and observation group by the random number table method, with 43 patients in each group. The control group was given conventional treatment, while the observation group was given supramolecular salicylic acid chemical peeling agent on the basis of the control group. The clinical efficacy, symptom relief time, skin barrier function, patient self-assessment, adverse reactions and recurrence were compared between the two groups. Results The total effective rate in the observation group was 93.02%, which was higher than 81.40% in the control group (P <0.05). The erythema regression time, swelling and pain regression time, incrustation time and decrustation time in the observation group were shorter than those in the control group (P <0.05). The transepidermal water loss in the observation group after treatment was lower than that in the control group, and the stratum corneum hydration was higher than that in the control group (P <0.05). The self-assessment of skin improvement in the observation group was higher than that 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 recurrence rate in the observation group was 4.65%, which was lower than 13.95% in the control group (P <0.05). Conclusion Supramolecular salicylic acid chemical peeling agent has high efficacy and safety, which can effectively promote the relief of clinical symptoms and improve the skin barrier function of patients. It is worthy of clinical application.