Hepatic dysfunction is primarily caused by nonalcoholic fatty liver disease (NAFLD). Recently, berberine (BBR) has attracted researchers’ interest with its hepatic protective property. A systematic review was conducted to evaluate the effects of BBR and its mechanisms of action in the management of NAFLD and its complications. The guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements were applied to perform the study. Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases were searched up until March 2023. According to the inclusion criteria, finally, 65 studies were entered into the study. The evidence provided in the study revealed that BBR could regulate the development of NAFLD via several mechanisms of action namely lowering body weight, modulating lipid and glucose metabolism, and reducing inflammation and oxidative stress (OS). The current systematic review demonstrated the beneficial effects of BBR on NAFLD and its associated metabolic disorders including dyslipidemia, obesity, and insulin resistance through regulating lipid metabolism, facilitating β-oxidation of fatty acids, and mitigating the accumulation of triglycerides in hepatocytes. These beneficial effects make BBR a potential therapeutic approach and an efficient agent in the management of NAFLD and its related risk factors. There is an insufficient number of clinical trials addressing the effects of BBR in humans, so conducting more human research in the future is recommended.