The aim of this study was to well understand the dynamic changes of physicochemical properties of polysaccharides from loquat leaves (LLP) during in vitro simulated saliva-gastrointestinal digestion and fecal fermentation and its related impacts on human gut microbiota. Results showed that the contents of reducing sugar of LLP slightly increased during the gastrointestinal digestion, and its molecular weight also slightly decreased, suggesting that LLP could be slightly degraded under the gastrointestinal digestion conditions. Moreover, during the fecal fermentation, the molecular weight of the indigestible LLP (LLP-I) significantly decreased, and the molar ratio of constituent monosaccharides of LLP-I, such as glucuronic acid, galacturonic acid, galactose, and arabinose, significantly changed, indicating that LLP-I could be degraded and consumed by human gut microbiota. Indeed, some beneficial bacteria such as Megasphaera, Megamonas, Bifidobacterium, Phascolarctobacterium, and Desulfovibrio significantly increased, suggesting that LLP-I could change the composition and abundance of gut microbiota. LLP-I could also promote the production of health-promoting short chain fatty acids. Results from this study are benefical to well understand the in vitro digestion and fecal fermentation behaviors of LLP, and LLP can be developed as a potential prebiotic in the functional food industry.