Background: Rheum tanguticum is utilized as one of the well known traditional Chinese medicine for the treatment of gastrointestinal diseases. Recently, R. tanguticum polysaccharides (RP) have received increasing attention due to their diversely pharmacological activities. Usually, the pharmacological activities of polysaccharides are closely correlated to their metabolic properties from the stomach to the intestine. However, the digestive behavior and fecal fermentation characteristics of RP are unknown, which need to be fully investigated. Methods: In this study, an in vitro simulated gastrointestinal model was carried out for the investigation of the digestive behavior and fecal fermentation characteristics of RP. The possible changes in physicochemical properties of RP, such as molecular weight, monosaccharide composition, reducing sugar released, chemical composition, pH value, and short chain fatty acids, were determined during in vitro simulated digestion and human fecal fermentation, and its effect on the modulation of gut microbial composition was also evaluated. Results: The results revealed that RP was indigestible under the in vitro simulated digestion conditions according to its stabilities in physicochemical properties. Conversely, the indigestible RP (RPI) could be notably utilized by colonic microbiota in human feces after the in vitro fermentation, especially, at the initial fermentation stage (0–6 h). The fecal fermentation characteristics of RPI were revealed. Results showed that the content of reducing sugars obviously increased from 0.177 to 0.778 mg/mL at the initial stage of fermentation, and its molecular weight notably declined from 2.588 × 10 to 0.828 × 10 Da at the end stage of fermentation. Notably, the utilization of arabinose and galactose in RPI by colonic bacteria was faster than that of galacturonic acid. Besides, RPI could obviously modulate gut microbial composition via promoting the relative abundances of several beneficial bacteria, such as genera Bacteroides, Bifidobacterium, and Megamonas, resulting in the promoted production of several short-chain fatty acids, such as acetic, propionic, and butyric acids. Conclusions: Results from this study showed that RP was indigestible in the human upper gastrointestinal tract in vitro, but could be easily utilized by colonic microbiota in human feces at the initial stage of fermentation. RP could be used as potential prebiotics for the improvement of intestinal health.