FGF21 is involved in main biological processions in human beings, and some clinical trials provided an initial advancement for human FGF21 analogs as a worthy therapeutic candidate in type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH) (Table 1). This evidence concerns the gene FGF21 and metabolic dysfunction-associated steatohepatitis.