Metabolic dysfunction-associated steatotic liver disease has emerged as a global public health concern. Fibroblast growth factor 21, a liver hormone, is gaining interest because of its ability to regulate metabolism and improve metabolic dysfunction-associated steatotic liver disease. In this network meta-analysis, we investigated the efficacy of these treatments in treating metabolic dysfunction-associated steatotic liver disease. A comprehensive search was conducted across electronic databases, including PubMed, Scopus, the Cochrane Library, and Web of Science, till August 2025. We used R software to analyze data using a random effects model. Heatmaps were used to visualize the included interventions' ranking. We included 9 clinical trials comprising 1277 patients. Among them, 284 received efruxifermin, 263 received pegbelfermin, 151 received pegozafermin, 65 received efimosfermin, 139 received MK-3655, and 375 received a placebo. Pegozafermin and efruxifermin were effective in improving liver fibrosis (RR, 3.89-3.93, P < .05; RR, 2.23-1.91, P < .05, respectively), whereas the other interventions did not yield statistical significance. Efimosfermin α, efruxifermin, and pegozafermin improved different metabolic parameters, including adiponectin, hemoglobin A1c, and non-high-density lipoprotein. However, no significant differences were observed in body weight and low-density lipoprotein. For liver enzymes, efimosfermin α had the greatest reduction of alanine aminotransferase and aspartate aminotransferase, whereas efruxifermin was most effective in reducing γ-glutamyl transferase levels. The odds of adverse events were higher in pegozafermin, efimosfermin, and efruxifermin groups, mainly attributed to mild to moderate gastrointestinal adverse events. In conclusion, efruxifermin and pegozafermin are promising therapeutic options with a tolerable adverse event profile; meanwhile, efimosfermin α showed promising results in improving metabolic parameters, with histologic results yet to be published. SIGNIFICANCE STATEMENT: This meta-analysis evaluates the efficacy of fibroblast growth factor 21 analogs in improving metabolic dysfunction-associated steatotic liver disease. Efruxifermin and pegozafermin were the most significant in improving liver fibrosis; moreover; significant improvements in some metabolic parameters were observed with efimosfermin α, efruxifermin, and pegozafermin.