The interaction of gut microbiota, related metabolites and inflammation factors with nonalcoholic fatty liver disease (NAFLD) remains unclearly defined. The aim of this systematic review and meta-analysis was to synthesize previous study findings to better understand this interaction. Relevant research articles published not later than September, 2019 were searched in the following databases: Web of Science, PubMed, Embase, and Cochrane Library. The search strategy and inclusion criteria for this study yielded a total of 47 studies, of which only 11 were eligible for meta-analysis. The narrative analysis of these articles found that there is interplay between the key gut microbiota, related metabolites and inflammation factors, which modulate the development and progression of NAFLD. In addition, the results of meta-analysis showed that probiotic supplementation significantly decreased tumor necrosis factor-α (TNF-α) in NAFLD patients (standardized mean difference (SMD) = -0.52, confidence interval (CI): -0.86 to -0.18, and p = 0.003) and C-reactive protein (CRP) (SMD = -0.62, CI: -0.80 to -0.43, and p < 0.001). However, whether therapies can target TNF-α and CRP in order treat NAFLD still needs further investigation. Therefore, these results suggest that the interaction of the key gut microbiota, related metabolites and inflammation factors with NAFLD may provide a novel therapeutic target for the clinical and pharmacological treatment of NAFLD.