Treatment with AuNP significantly lowered the BG level, the gene expression, and the activity of hepatic PEPCK in comparison with the untreated diabetic group. The AuNPs synthesised can alleviate HYG in HFD/STZ-induced diabetes in rats by reducing hepatic gluconeogenesis by inhibiting the expression and activity of the hepatic PEPCK gene. This evidence concerns the gene PCK2 and diabetes mellitus.