Objective To analyze the effect of supramolecular salicylic acid combined with minocycline on skin barrier function and symptom scores in patients with papulopustular rosacea. Methods A total of 60 patients with papulopustular rosacea admitted to Changsha Kefanmei Medical Aesthetic Clinic from January 2022 to December 2023 were selected, and they were divided into the control group and the observation group by the random number table method, with 30 patients in each group. The control group was treated with minocycline, and the observation group was treated with supramolecular salicylic acid on the basis of the control group. The clinical efffcacy, symptom scores, skin barrier function indicators, adverse reaction rate and recurrence rate were compared between the two groups. Results The total effective rate of treatment in the observation group (90.00%) was higher than that in the control group (70.00%) (P<0.05). After treatment, the symptom scores of the observation group were lower than those of the control group (P<0.05). After treatment, the skin barrier function indicators of the observation group were better than those of the control group (P<0.05). There was no statistically signiffcant difference in the incidence of adverse reactions between the two groups (P>0.05). The recurrence rate of the observation group (6.67%) was lower than that of the control group (26.67%) (P<0.05). Conclusion The application of supramolecular salicylic acid combined with minocycline in patients with papulopustular rosacea can effectively improve the clinical effect, enhance skin barrier function, reduce the recurrence rate, and has relatively good safety.