Objective To observe the effectiveness of isotretinoin and compound polymyxin B ointment combined with red and blue light in the treatment of acne vulgaris and the effects on serum dehydroisoandrosterone (DHEA) and interleukin-17A (IL-17A) levels.Methods Ninety-six patients with common acne admitted to the Department of Dermatology of our hospital from January 2022 to June 2024 were selected and divided into 48 cases in the isotretinoin group and 48 cases in the comprehensive group using the random number table method. Both groups were treated with red and blue light, isotretinoin was given to the isotretinoin group, and compound polymyxin B ointment was given to the comprehensive group on the basis of the isotretinoin group for 4 weeks. The differences in serum DHEA, IL-17A, interleukin-17 (IL-17), tumour necrosis factor-α (TNF-α), skin physiological indexes [sebum secretion, skin transdermal water loss (TEWL)], and parameters of VISIA facial image analysis (pores, facial red areas, purple matter, brown spots) were detected before and after treatment, and the clinical efficacy and adverse reactions of the two groups were counted. Results There was no difference in the comparison of DHEA, IL-17A, IL-17, and TNF-α between the two groups before treatment (P>0.05). DHEA, IL-17A, IL-17, and TNF-α decreased in both groups after treatment, but the above serum indexes were lower in the combined group than in the isotretinoin group after treatment (P<0.05). There was no difference in the comparison of skin physiological indexes and VISIA facial image analysis parameters between the two groups before treatment (P>0.05). Sebum secretion, TEWL, and VISIA facial image analysis parameters (pores, facial red areas, purple matter, and brown spots) decreased in both groups after treatment, but skin physiological indexes and VISIA facial image analysis parameters were lower in the comprehensive group than in the isotretinoin group after treatment (P<0.05). The total effective rate of the comprehensive group was higher than that of the isotretinoin group, but there was no difference in the rate of adverse reactions compared with that of the isotretinoin group (P>0.05).Conclusion Isotretinoin and compound polymyxin B ointment combined with red and blue light in the treatment of common acne improves skin physiological indices and inhibits the expression of DHEA, IL-17A, IL-17, and TNF-α, which improves the efficacy of the treatment without increasing the adverse effects.