Abstract: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The prevalence of NAFLD is increasing year by year in the world, which seriously threaten the public health. The pathogenesis of NAFLD is complex, and there is no specific treatment for NAFLD. Natural-derived compounds have the characteristics of multi-target and multi-mechanism, which can improve the curative effect and reduce the toxic and side effects by regulating multiple factors of the disease. They are ideal drugs for treating complex diseases and have unique advantages in improving NAFLD. However, low intestinal absorption, poor bioavailability, and single medicine efficiency limit the utilization of many compounds, and further drug development and clinical application are challenging. This paper reviews the research progress of natural-derived compounds in the prevention and treatment of NAFLD in recent years, analyzes the existing problems, and discusses the improvement strategies, so as to provide reference for related research.