PurposeThe hyperproliferation of C. acnes has long been regarded as a primary etiological factor in the development of acne vulgaris (AV). Antibiotics targeting C. acnes have been the mainstay in AV treatment. Meanwhile, C. acnes has developed resistance to numerous antibiotics. IDDS, as traditional Chinese medicine, exhibits potent antibacterial activity against C. acnes. However, the mechanism of IDDS against C. acnes remains unclear.MethodsIn this study, we conducted a systematic investigation in vitro to determine the minimal bactericidal concentration (MBC) and time-kill curves. The MBC and time-kill curves were assessed by quantifying Colony Forming Units countsIn order to establish an in vivo rat ear model of acne, a single intradermal injection of 100μL C. acnes suspension was administered, and oleic acid was applied to the right ear pinna for a duration of 14 days. The intervention involved the utilization of IDDS medications. Additionally, the levels of inflammatory mediators tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) were assessed using respective ELISA kits, while Hematoxylin and eosin (HE) staining was employed to visualize the rat ear model. The antimicrobial mechanism was investigated through the analysis of mRNA levels using real-time, quantitative PCR. ELISA analysis was performed according to the protocols outlined for energy metabolism and antioxidant system.ResultsOur research has demonstrated that IDDS possesses antibacterial activity against C. acnes both in vitro and in vivo. The mechanisms underlying these effects involve energy metabolism and antioxidant systems.ConclusionThe data has provided further insights into the mechanism of IDDS against C. acnes, which establishes a robust foundation for the clinical application of IDDS.