In conclusion, this study demonstrates that (+)-dehydrovomifoliol protects hepatocytes against OA-induced lipid accumulation through activation of the PPARα–FGF21 pathway and hence encourages the future use of (+)-dehydrovomifoliol derivatives for the prevention and/or treatment of NAFLD and NASH and their complications. This evidence concerns the gene PPARA and metabolic dysfunction-associated steatohepatitis.