Background: Floccularia luteovirens (Alb. & Schwein.) Pouzar, is an extremely rare edible and medicinal mushroom in China. The crude polysaccharides of F. luteovirens (FLPs) has significant antioxidant and anti-inflammation activities and exerts excellent protective functions in diabetic nephropathy (DN) complications, but the material basis of the pharmacological effects of FLPs and the molecular mechanism of its pharmacological action are still unclear. Methods: First, we performed systemic composition analysis on extracted and isolated FLPs. Next, the spontaneous db/db mouse DN model was used to investigate the mitigation and protection functions of FLPs in DN and the underlying mechanism through the mammalian target of the rapamycin (mTOR)/GSK-3\beta/NRF-2 pathway. Results: FLPs contained 65.0% total sugars, 7.2% reducing sugars, 7.93% proteins, 0.36% total flavonoids, 17 amino acids, 13 fatty acids, and 8 minerals. After intragastric administration of FLPs with concentrations of 100, 200 and 400 mg/kg for 8 weeks, FLPs inhibited excessive weight gain, relieved the symptoms of obesity, and significantly improved glucose metabolism and lipid metabolism in the db/db mice. In addition, FLPs were also involved in regulating the indicators of various oxidases and inflammatory factors in the serum and kidney of db/db mice. Conclusions: FLPs effectively improved and relieved kidney tissue injury caused by high glucose, targeted and regulated phospho-GSK-3\beta, and suppressed inflammatory factor accumulation. Furthermore, FLPs activated the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (NRF2/HO-1) pathway and enhanced the activity of catalase (CAT) to further play a role in relieving and treating T2DM and nephropathy complications.