Objective: To investigate the effect of Huanglian Jiedu Decoction combined with probiotic supplement on serum leptin (Leptin, LEP) levels and liver fibrosis indicators in patients with non-alcoholic steatohepatitis (Non-alcoholic steatohepatitis, NASH). Methods: A total of 82 patients with NASH admitted to the hospital from May 2022 to July 2024 were selected. They were divided into the control group (41 cases) and the observation group (41 cases) by stratified randomization. The former was treated with live Bifidobacterium capsule alone, while the latter was treated with Huanglian Jiedu Decoction combined with live Bifidobacterium capsule. The clinical efficacy, LEP, liver function indicators, liver fibrosis indicators, and incidence of adverse reactions were compared between the two groups. Results: Compared with the control group, the observation group showed a higher overall response rate (85.37% vs. 100%, P<0.05), and lower levels of LEP and liver function indicators (P<0.05). No statistically significant difference in liver fibrosis indicators was observed between the two groups (P>0.05). The total incidence rates of adverse reactions in the control group and the observation group were 2.44% and 9.76%, demonstrating no statistically significant difference (P>0.05). Conclusion: Compared to treatment with live Bifidobacterium capsule alone, combined treatment with Huanglian Jiedu Decoction and live Bifidobacterium capsule achieves a higher clinical response rate. Moreover, it can improve LEP and liver function indicators, and prevent liver fibrosis lesions in patients with NASH, without significant increase in safety risk.