Objective To investigate the clinical effect of Niubang Jieji Decoction combined with Yiyi Fuzi Baijiang Powder in the treatment of acne with spleen-stomach damp-heat. Methods A total of 47 patients with acne with spleen-stomach damp-heat were randomly divided into control group with 23 patients and treatment group with 24 patients. The patients in the treatment group were given oral administration of Niubang Jieji Decoction combined with Yiyi Fuzi Baijiang Powder, and those in the control group were given oral administration of Pudilan Xiaoyan Tablet. The course of treatment was 8 weeks for both groups. Clinical outcome was evaluated every 4 weeks, and the global acne grading system (GAGS) score was determined for each patient. Results At the end of weeks 4 and 8 of treatment, there was a significant difference in clinical outcome between the two groups (P<0.05), and the treatment group had a better clinical outcome than the control group. Both groups had a significant reduction in GAGS score after treatment (P<0.05), and the treatment group had a significantly lower GAGS score than the control group(P<0.05). Conclusion Niubang Jieji Decoction combined with Yiyi Fuzi Baijiang Powder has a good clinical effect in the treatment of acne with spleen-stomach damp-heat.