Objective To explore the effect of compound glycyrrhizin combined with hydroxychloroquine sulfate on skin improvement and skin barrier function in patients with rosacea. Methods A total of 60 patients with rosacea admitted to the Department of Dermatology, Guilin Maternal and Child Health Hospital from April 2023 to May 2025 were selected as the research subjects. According to the random number table method, they were divided into the control group and the study group, with 30 patients in each group. The control group was treated with hydroxychloroquine sulfate, and the study group was treated with compound glycyrrhizin combined with hydroxychloroquine sulfate. The skin improvement effect, skin barrier function, serum inffammatory factor levels and adverse reaction rate were compared between the two groups. Results The total effective rate of skin improvement in the study group (93.33%) was higher than that in the control group (73.33%) (P<0.05). At 3 months after treatment, the TEWL of the study group was lower than that of the control group, and the SCH was higher than that of the control group (P<0.05). At 3 months after treatment, the levels of TNF-α and IL-6 in the study group were lower than those in the control group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion The combined treatment of compound glycyrrhizin and hydroxychloroquine sulfate for patients with rosacea can effectively improve the overall skin improvement effect, enhance skin barrier function, promote inffammation control, and the combined medication does not increase the risk of adverse reactions.