The modern rise in type 2 diabetes mellitus (T2DM) and its correlation to commensal microbiota have elicited global concern about the patterns of microbial action in the host. With the exception of that linked to gut, microbiota were also colonized in pancreas, oral, and lung, contributing to the physiopathology of T2DM. In this study, we aimed to explore the protective effects of Ganoderma atrum polysaccharide (PSG) and White Hyacinth Bean polysaccharide (WHBP) on the intestine, pancreas, oral, and lung microbiota in T2DM rats. Here we showed that, despite capacities of polysaccharides that exerted similar protective effects on hyperglycemia, dyslipidemia, insulin resistance and dysbacteriosis in T2DM rats, PSG and WHBP were able to be characterized by their own "target" bacteria, which could be proposed for activity-fingerprinting of polysaccharide species. Furthermore, we found a mutual bacteria spectrum in the pancreas and lung, and most bacteria could be tracked to oral or gut samples. Notably, the overlapping areas of the microbiota profile between organs (pancreas, lung) and saliva were more than in the gut, suggesting that a saliva sample was also of interest to serve as a "telltale sign" for judging pancreatic injury. Together, these microbiota interactions provided a new potential to harvest alternative samples for disease surveillance. Meanwhile, polysaccharides had anti-T2DM abilities, which could be distinguished by their own characteristic bacteria.