Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease characterized with the spectrum of hepatic steatosis, inflammation, and fibrosis. The etiology of NAFLD remains incompletely understood. Numerous studies have implied that the gut microbiota (GM) is involved in the development of NAFLD, as it particularly mediating the interaction between nutrient intake and the gut-liver function. Meanwhile, the omega-3 and omega-6 polyunsaturated fatty acids (n-3/n-6 PUFA) as essential fatty acids have been linked to NAFLD. Increasing studies in the past decades have indicated that there is a reciprocal interaction between GM and n-3/n-6 PUFA, which may be underlying at least in part, the pathogenesis of NAFLD. In this review, we will discuss: (1) How GM is linked to NAFLD by interacting with various nutrients; (2) How imbalanced dietary n-3/n-6 PUFA is linked to NAFLD; (3) How n-3/n-6 PUFA may affect the GM balance, leading to altered nutrients release to the liver; and (4) How GM may modify ingested n-3/n-6 PUFA and alter their absorption, bioavailability, and biotransformation.