Objective: To observe the clinical efficacy of Zhitong Danshu Decoction combined with wet-hot compress with Danzhang San in the treatment of mild to moderate acute cholecystitis of liver and gallbladder damp-heat pattern. Methods: A total of 80 patients with mild to moderate acute cholecystitis of liver and gallbladder damp-heat pattern who were treated in the hospital from January 2023 to July 2025 were selected and divided into two groups by random number table method. The control group received conventional Western medicine treatment, while the observation group was treated with Zhitong Danshu Decoction combined with wet-hot compress with Danzhang San based on the control group"s regimen. Traditional Chinese medicine (TCM) syndrome scores, Visual Analogue Scale (VAS) scores of abdominal pain, inflammation-related indicators (C-reactive protein (CRP), procalcitonin (PCT), white blood cell count (WBC), neutrophil ratio (N%)), and efficacy were compared between the two groups. Results: The total effective rate in the observation group was 97.50%, significantly higher than 80.00% in the control group (P<0.05). After treatment, both groups showed significant reductions in the scores for main and secondary TCM syndromes, CRP, WBC, PCT, N%, and VAS score of abdominal pain compared to those before treatment (P<0.05). Moreover, above indicators in the observation group were significantly lower than those in the control group (P<0.05). Conclusion: Applying Zhitong Danshu Decoction combined with wet-hot compress with Danzhang San in the treatment of mild to moderate acute cholecystitis of liver and gallbladder damp-heat pattern can effectively alleviate TCM syndromes, reduce inflammation level, and improve clinical efficacy.