Objective To explore the mechanism of GS-9620 in improving imiquimod (IMQ)-induced psoriasis-like inflammation by regulating the Th1/Th17-related immune response, and to investigate its regulatory effect on the gut microbiota in mice. Methods An IMQ-induced psoriasis-like inflammation model was established in BALB/c mice. The severity of the skin lesions was evaluated by psoriasis area and severity index (PASI) score. The proportions of CD4⁺ interleukin (IL)-17⁺ and CD4⁺ interferon (IFN)-γ⁺ cells in spleen tissue were detected by flow cytometry. Levels of the inflammatory factors tumor necrosis factor (TNF)-α, IL-1β, and IL-6 in skin tissues were determined by enzyme-linked immunosorbent assay, and pathological analysis was performed by hematoxylin/eosin staining. The effects of GS-9620 on the structure of the gut microbiota in control, IMQ model, and GS-9620-treated mice were detected by 16S rRNA sequencing. Results GS-9620 significantly reduced the PASI score in IMQinduced mice and effectively reduced the proportions of CD4⁺ IL-17⁺ and CD4⁺ IFN-γ⁺ cells in the spleen. GS-9620 also significantly down-regulated the expression levels of TNF-α, IL-1β, and IL-6 in skin tissues. 16S rRNA sequencing showed that GS-9620 significantly regulated the abundance of gut microbiota related to inflammation, including the relative abundances of bacteria such as Lachnospiraceae_NK4A136_group, Lachnospiraceae_UCG-008, Alloprevotella, Desulfovibrio, Prevotellaceae_UCG-001, and Alistipes. Conclusions GS-9620 effectively alleviates IMQ-induced psoriasis-like skin inflammation in mice by regulating the expression of Th1/Th17-related inflammatory factors. It may also improve IMQ-induced clinical symptoms by regulating the structure of the gut microbiota, thus providing a new theoretical basis for the treatment of psoriasis. The result of this study provide important experimental evidence to support further investigations into the application of GS-9620 for the treatment of psoriasis.