Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of end-stage liver disease, leading to a rapidly growing global public health burden. The term “gut microbiome (GM)” refers to the approximately 100 trillion microbial cells that inhabit the host’s gastrointestinal tract. There is increasing evidence that GM is involved in the pathogenesis of NAFLD and may be a potential target for intervention. To explore GM-based strategies for precise diagnosis and treatment of NAFLD, great efforts have been made to develop a comprehensive and in-depth understanding of the host–microbe interaction. This review evaluates this interaction critically, mainly considering the intricate regulation of the metabolism, immunity, and inflammatory status during the evolution of the disease pathogenesis, revealing roles for the GM in NAFLD by examining advances in potential mechanisms, diagnostics, and modulation strategies.