Previous studies have shown that prolamin from cooked foxtail millet(PCFM) can effectively improve glucose metabolism disturbances in high-fat diet and streptozotocin-induced diabetic mice. The current study aimed to investigate the molecular mechanism by which PCFM enhances glucose metabolism， focusing on liver transcriptomics. The results showed that， compared to the control group， the livers of mice treated with PCFM exhibited significant up-regulation of 1 758 differentially expressed genes and down-regulation of 198 genes. KEGG functional annotation analysis revealed that these genes were associated with pathways related to lipid and carbohydrate metabolism. Furthermore， the KEGG pathway enrichment analysis highlighted the phosphoinositide-3 kinase(PI3K)/protein kinase B(AKT) signaling pathway as the most significantly enriched pathway involved in glucose metabolism， with 27 genes up-regulated and one down-regulated after PCFM intervention. This study aims to elucidate the molecular mechanisms underlying the hypoglycemic effects of PCFM and provide a foundation for the development of functional foods targeting hypoglycemia.