Background: Modification of the gut microbiota may be a novel therapeutic target for nonalcoholic fatty liver disease (NAFLD), according to earlier research that demonstrated the encouraging benefits of gut microbiome-targeted therapeutics (MTTs). Aim: This meta-analysis study aimed to determine the impact of microbiome-targeted therapies on NAFLD patients, highlighting similarities and differences in reported clinical outcomes. Methods: A search across PubMed, Scopus, Web of Science, and the Cochrane Library for: Microbiome-targeted treatments, probiotics, synbiotics, and prebiotics for randomized controlled trials (RCTs) that included individuals with non-alcoholic fatty liver disease (NAFLD) and compared MTT to normal care or a placebo. Results: The meta-analysis, including seven studies with a total of 430 participants, found that probiotics, synbiotics, and other pharmacological agents like rifaximin and sitagliptin-synbiotics demonstrated varying degrees of efficacy in improving liver function, reducing inflammatory markers, and managing associated comorbidities. Probiotic treatments, while generally safe, well-tolerated, and cost-effective, have shown promising results in reducing liver enzymes, improving insulin resistance, and modulating inflammatory cytokines. Synbiotics, particularly when combined with sitagliptin, have been found to produce superior results in managing glycemic control and lipoprotein levels compared to placebo treatments. Similarly, rifaximin therapy has demonstrated significant reductions in endotoxin levels, proinflammatory cytokines, and liver fat scores, highlighting its potential as an adjunctive treatment for nonalcoholic steatohepatitis (NASH). Conclusion: Although encouraging, larger-scale studies with longer follow-up times are needed to fully investigate the therapeutic utility of probiotics, synbiotics, and adjuvant therapies in order to develop clear clinical guidelines for their application in the therapy of NASH and NAFLD.