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Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than a third of the world’s adult population, making it a daunting health concern. Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced subtype of MASLD. MASH prevalence is increasing exponentially and carries a high risk for disease progression, cirrhosis, and liver-related mortality. Aldafermin, a fibroblast growth factor 19 (FGF19) analog, is one of the evolving therapeutic agents with the potential to regulate multiple pathways involved in the pathogenesis of MASH. We aimed to investigate the efficacy and safety of aldafermin in patients with MASH.Methods PubMed, Scopus, Cochrane Library, and Web of Science were searched to identify eligible randomized controlled trials (RCTs). The meta-analysis was conducted using RevMan. Continuous data were pooled as mean difference (MD), while dichotomous data were pooled as risk ratios (RR) with a 95 % confidence interval. A subgroup meta-analysis was conducted to evaluate the efficacy of the two doses of aldafermin (1 mg and 3 mg). Risk of bias was assessed using the Cochrane RoB 2 tool.Results Four phase 2 RCTs with a total of 491 patients were included. All studies were found to have a low risk of bias. Aldafermin showed a dose-dependent improvement in the ≥ 30 % reduction in the liver fat content (RR: 2.16, 95 % CI [1.41 to 3.32]) and (RR: 5.00, 95 % CI [1.34 to 18.64]), alanine aminotransferase levels (MD: −19.79, 95 % CI [−30.28 to −9.3]) and (MD: −21.91, 95 % CI [−29.62 to −14.21]), aspartate aminotransferase levels (MD: −11.79, 95 % CI [−18.06 to −5.51]) and (MD: −13.9, 95 % CI [−18.59 to −9.21]), and enhanced liver fibrosis score (ELF) (MD: −0.13, 95 % CI [−0.29 to 0.02]) and (MD: −0.33, 95 % CI [−0.50 to −0.17]), in the 1 mg and 3 mg subgroups respectively. No significant differences were detected in the aldafermin group regarding histologic endpoints, lipid profile, metabolic parameters, and overall adverse effects, except for the increased occurrence of diarrhea in the aldafermin 3 mg subgroup.Conclusion Aldafermin is a promising well-tolerated therapeutic agent for MASH with evidence supporting its ability to reduce liver fat content, fibrosis serum biomarkers, and liver enzymes. However, its effectiveness in improving histologic fibrosis, while showing numerical trends, still lacks statistical significance. Larger and longer MASH trials are warranted to enhance the robustness of the evidence.