Abstract: Objective To investigate the mechanism of Qiwei Baizhu powder in the treatment of glucose metabolism disorder in type 2 diabetes mellitus (T2DM) based on network pharmacology and animal experiments. Methods The active ingredients and targets of Qiwei Baizhu powder were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and T2DM-related targets were obtained from GeneCard, OMIM and DisGeNET databases. Protein-protein interaction (PPI) analysis was performed using STRING and CytoScape to screen key targets. The key targets were applied for GO and KEGG enrichment analysis through the DAVID platform. Molecular docking was conducted to verify the binding of active ingredients to key targets. A rat model of T2DM was established, and fasting blood glucose and insulin levels were detected by HE staining and oil red O staining. The levels of p-AKT1, HIF1α, IL-6 and IL-1β in liver tissues were detected by Western blot. Results A total of 96 potential targets of Qiwei Baizhu powder for improving glucose metabolism disorder in T2DM were obtained, and the top 21 key targets were selected by PPI network analysis. GO enrichment analysis identified 72 GO terms, and KEGG enrichment analysis revealed 86 signaling pathways. Molecular docking results showed that active ingredients, such as quercetin, kaempferol, naringenin, and β-sitosterol, had lower binding energy and more stable structures with the key targets. According to animal experiments, Qiwei Baizhu powder decreased blood glucose, improved insulin resistance, alleviated pancreatic tissue injury and lipid droplet accumulation in the liver, and decreased the levels of p-AKT1, HIF1α, IL-6 and IL-1β (P<0.001). Conclusions Qiwei Baizhu powder has the characteristics of multi-component, multi-target and multi-pathway for improving glucose metabolism disorder in T2DM rats. It can reduce blood glucose, improve insulin resistance, and reduce the levels of p-AKT1, HIF1α, IL-6 and IL-1β in T2DM rats, which may be related to the major pathways such as the IL-17 pathway and the HIF1α pathway.