Fomes fomentarius is a medicinal fungus used in traditional Chinese medicine to treat various illnesses. Antidiabetic effects of F. fomentarius extracts have been reported recently. In this study, F. fomentarius extracellular polysaccharide (PS) was prepared, and then to enhance its antidiabetic effects, Na2SeO3 was added to the culture medium, and selenium-polysaccharide (PS-Se) was obtained. Also, solid lipid nanoparticles containing PS (SLN-PS) and PS-Se (SLN-PS-Se) were synthesized by the microemulsion method to compare their effects with free polysaccharides in streptozotocin (STZ) diabetic rats. Optimized SLNs had a size of 170.5nm and drug loading of 9.27%. EDS analysis confirmed that Se presence in PS-Se. Characterization analyses such as FTIR, DSC, TGA, and XRD suggested that SLNs have good thermal stability and crystalline nature. Release of PS from SLNs demonstrated sustained profile, and MTT assay proved that PSs and SLNs have no cytotoxicity. Furthermore, oral administration of PS, PS-Se, SLN-PS, and SLN-PS-Se for 28days to diabetic rats significantly declined blood glucose by 48.24%, 49.96%, 55.50%, and 60.47%, respectively. Also, insulin secretion and body weight improved, and HbA1c levels decreased. Treatment by PS, PS-Se, SLN-PS, and SLN-PS-Se alleviated lipid profiles, liver enzymes, and serum proteins. Liver anti-oxidant parameters and histopathological observation of the liver, pancreas, and kidney confirmed that F. fomentarius PSs and SLNs have antidiabetic impacts. Moreover, supplementation of PS with selenium improves its anti-hyperglycemic effects. Finally, SLN-PS and SLN-PS-Se showed a higher antidiabetic impact than free PS and PS-Se.