Objective To observe the effect of red and blue light combined with supramolecular salicylic acid on serum IL-6 level and sebum secretion in patients with moderate to severe acne. Methods A total of 92 patients with moderate to severe acne admitted to the Department of Dermatology, Gaoyou People's Hospital from January 2022 to December 2025 were selected, and they were divided into the control group and the observation group by the random number table method, with 46 patients in each group. The control group was treated with red and blue light, and the observation group was treated with red and blue light combined with supramolecular salicylic acid. The clinical efficacy, serum IL-6 level, sebum secretion and acne severity were compared between the two groups. Results The total effective rate of the observation group (91.30%) was higher than that of the control group (76.09%) (P<0.05). At 8 weeks after treatment, the IL-6 level and sebum secretion in the two groups were lower than those before treatment, and those in the observation group were lower than those in the control group (P<0.05). At 8 weeks after treatment, the GAGS score of the two groups was lower than that before treatment, and that of the observation group was lower than that of the control group (P <0.05). Conclusion The application of red and blue light combined with supramolecular salicylic acid in the treatment of patients with moderate to severe acne can improve therapeutic efficacy, inhibit IL-6 expression, regulate sebum secretion, and reduce acne severity, which possesses definite clinical application value.