The present disclosure relates to a human FGF21 mutant with improved effectiveness and stability, preparation method and pharmaceutical composition comprising the mutant, and a use thereof, and specifically relates to a human fibroblast growth factor 21 (FGF21) mutant, a gene encoding the same, and a method for preparing the mutant and a method of using the mutant for treating type 2 diabetes, obesity, dyslipidemia, or metabolic disorders.