OBJECTIVE: With a steadily rising prevalence, nonalcoholic fatty liver disease (NAFLD) was a leading global cause of liver-related health problems. In the clinical management of NAFLD, various western pharmaceuticals were widely utilized. This network meta-analysis aimed to evaluate the effectiveness of common western medications for NAFLD patients. METHODS: We systematically reviewed and screened articles based on predesigned criterion about western medications for NAFLD, which were from Embase, Cochrane Library, PubMed, CNKI, WanFang, and China Science and Technology Journal Database until August 1, 2024. Eligible studies included randomized controlled trials of patients aged 18 or older with NAFLD, comparing Western medicines to placebos or other Western medicine treatments. The risk of bias assessment tool 2.0 from the Cochrane system was used to assess the quality of the included articles. A Bayesian network meta-analysis was conducted using WinBUGS 1.4.3 with a random-effects model and Markov Chain Monte Carlo methods. Treatment rankings were based on Surface Under the Cumulative Ranking Curve (SUCRA) values, and heterogeneity was assessed with I RESULTS: Based on 37 included articles involving 7673 patients, pioglitazone demonstrated the most significant effects in resolving nonalcoholic steatohepatitis without worsening fibrosis, increasing high-density lipoprotein cholesterol levels, and achieving a ≥ 2-point reduction in NAFLD activity scores (odds ratio [OR] = 0.09, 95% confidence interval [CI]: 0.01 to 0.81), with a SUCRA probability of 91.4%. Aldafermin showed remarkable effects in improving liver function markers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transpeptidase, with cumulative probabilities of 90% for ALT and 69.8% for AST. Cluster analysis revealed that Resmetirom and Aldafermin were superior options for enhancing liver function, while pioglitazone emerged as the best treatment for the comprehensive improvement of NAFLD. CONCLUSIONS: Pioglitazone outperformed other western medicines in terms of overall efficacy when treating NAFLD, but Aldafermin and Resmetirom showed superior improvement in liver function. This study provided a certain level of support for the use of specific clinical medications.