Objective: To analyze the clinical therapeutic effect of Boleda supramolecular salicylic acid topical application combined with minocycline on papulopustular rosacea, as well as the influence of this method on the skin barrier function and serum inflammatory factor levels of patients. Methods: A total of 120 patients with papulopustular rosacea admitted to the dermatology department of our hospital from January 2022 to December 2023 were selected and divided into a control group and an observation group by random number table method, with 60 cases in each group. The control group was treated with oral minocycline, while the observation group was combined with the external application of Boleda supramolecular salicylic acid on the basis of the control group. Both groups needed continuous treatment for 8 weeks. Compare the clinical efficacy of the two groups; Symptom score Skin barrier function indicators; Incidence of adverse reactions and recurrence rate. Result: The total clinical effective rate of the observation group was higher than that of the control group (P < 0.05). After 8 weeks of treatment, the symptom score of the observation group was lower than that of the control group (P < 0.05). The skin barrier function indicators of the observation group were all better than those of the control group (P < 0.05). Comparison of the incidence of adverse reactions between the two groups (P > 0.05); After a 3-month follow-up, the recurrence rate of the observation group was lower than that of the control group (P < 0.05). Conclusion: Oral administration of Boleda supramolecular salicylic acid combined with minocycline for the treatment of patients with papulopustular rosacea can effectively improve the clinical efficacy of patients, enhance the skin barrier function, reduce the recurrence rate, and has relatively good safety.