BackgroundMedicinal and food homologous plants (MFHPs) which can improve Type 2 Diabetes Mellitus (T2DM) draw significant attention among the public due to their low toxicity and more safety. Polysaccharides, one of the various active components of MFHPs, are recognized as effective modulators of the intestinal flora. By altering the composition of intestinal flora and affecting their metabolic products, polysaccharides can improve T2DM, making them a central focus of anti-diabetic research. PurposeThe purpose of this study is to systematically review the mechanism by which polysaccharides from MFHPs (MFHPPs) regulate the composition of intestinal flora and its metabolic products to improve T2DM. MethodsThis study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and conducts a comprehensive search on the PubMed, Web of Science and Embase databases. All experimental articles published up to March 4, 2024, are included in the search. ResultsAmong the 5733 articles reviewed, 29 were selected, covering 22 different MFHPs. MFHPPs can improve T2DM, particularly in lowering blood glucose levels, with consistent results. MFHPPs can regulate the diversity of intestinal flora in T2DM animal models, primarily affecting four phyla: decreasing Firmicutes and Proteobacteria while increasing Bacteroidetes and Actinobacteriota. At the genus level, the improvement of T2DM by MFHPPs is associated with the modulation of 12 key genera: Allobaculum, Akkermansia, Bifidobacterium, Lactobacillus, Helicobacter, Halomonas, Olsenella, Oscillospira, Shigella, Escherichia-Shigella, Romboutsia and Bacteroides. At the molecular level, MFHPPs primarily act by modulating the intestinal flora to increase short-chain fatty acid levels, promote the secretion of glucagon-like peptide-1, influence the IGF1/PI3K/AKT signaling pathway, or the PI3K/AKT/GSK-3β pathway, to lower blood glucose levels. They may also improve T2DM by working in glucose metabolism through the "microbiota-gut-organ" axis. MFHPPs can also alleviate T2DM by mitigating inflammation and oxidative stress: MFHPPs regulate intestinal flora to reduce lipopolysaccharide "leakage" and enhance intestinal mucosal permeability to tackle the inflammation associated with T2DM; MFHPPs enhance the expression of oxidative stress-related enzymes to alleviate oxidative stress and improve T2DM. Lastly, from a metabolic pathway perspective, MFHPPs are primarily involved in the metabolism of amino acids and their derivatives, carbohydrate metabolism and glutathione metabolism. ConclusionMFHPPs can improve T2DM by enhancing the composition of intestinal flora, regulating its metabolic products to promote insulin secretion, inhibiting glucagon-like peptide secretion, facilitating glycogen synthesis, reducing inflammation levels and alleviating oxidative stress. Furthermore, MFHPPs demonstrate potential protective effects on critical organs such as the pancreas, liver, kidneys and heart. Therefore, MFHPPs demonstrate significant clinical potential. However, most studies can only indicate the potential of MFHPPs intervention in improving T2DM through the intestinal flora. The causality between MFHPPs regulating the intestinal flora and T2DM requires further investigation.