In summary, we demonstrated that human UC-MSC infusions significantly attenuated hyperglycaemia, improved lipid metabolism, and ameliorated NAFLD in db/db mice, which may be associated with the upregulation of the HNF4α-CES2 pathway that promoted β-oxidation and inhibited lipogenesis in the liver. This evidence concerns the gene HNF4A and metabolic dysfunction-associated steatotic liver disease.