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Context Nonalcoholic fatty liver disease (NAFLD) is considered the leading cause of chronic liver disease worldwide. To date, no confirmed medication is available for the treatment of NAFLD. Previous studies showed the promising effects of gut microbiome–targeted therapies; however, the results were controversial and the strength of the evidence and their clinical significance remained unclear. Objectives This umbrella study summarizes the results of meta-analyses investigating the effects of probiotics, prebiotics, and synbiotics on liver enzymes in the NAFLD population. Data Source A comprehensive search of the PubMed, Scopus, Web of Science, and Cochrane Library databases was done up to December 20, 2022, to find meta-analyses on randomized control trials reporting the effects of gut microbial therapy on patients with NAFLD. Data Extraction Two independent investigators extracted data on the characteristics of meta-analyses, and any discrepancies were resolved by a third researcher. The AMSTAR2 checklist was used for evaluating the quality of studies. Data Analysis A final total of 15 studies were included in the analysis. Results showed that microbiome-targeted therapies could significantly reduce levels of alanine aminotransferase (ALT; effect size [ES], −10.21; 95% confidence interval [CI], −13.29, −7.14; P < 0.001), aspartate aminotransferase (AST; ES, −8.86; 95%CI, −11.39, −6.32; P < 0.001), and γ-glutamyltransferase (ES, −5.56; 95%CI, −7.92, −3.31; P < 0.001) in patients with NAFLD. Results of subgroup analysis based on intervention showed probiotics could significantly reduce levels of AST (ES, −8.69; 95%CI, −11.01, −6.37; P < 0.001) and ALT (ES, −9.82; 95%CI, −11.59, −8.05; P < 0.001). Synbiotics could significantly reduce levels of AST (ES, −11.40; 95%CI, −13.91, −8.88; P < 0.001) and ALT (ES, −11.87; 95%CI, −13.80, −9.95; P < 0.001). Prebiotics had no significant effects on AST and ALT levels (ES, −2.96; 95%CI, −8.12, 2.18, P = 0.259; and ES, −4.69; 95%CI, −13.53, 4.15, P = 0.299, respectively). Conclusion Gut microbiome–targeted therapies could be a promising therapeutic approach in the improvement of hepatic damage in patients with NAFLD. However, more studies are needed to better determine the best bacterial strains, duration of treatment, and optimum dosage of gut microbiome–targeted therapies in the treatment of the NAFLD population. Systematic Review Registration PROSPERO registration no. CRD42022346998. [ABSTRACT FROM AUTHOR]