This study investigated the effects of PGPs (Pleurotus geesteranus polysaccharides), a glucopyranose isolated from the mycelium of Pleurotus geesteranus and characterized with the main chain of →4)-α-D-Glcp-(1→, on the prevention against alcohol liver diseases (ALD), with the aim of providing a theoretical basis for the application of P. geesteranus as prebiotic agents in preventing and treating gut dysbiosis and alcohol-related metabolic disorders in individuals with ALD. The results showed that PGP treatment reduced oxidative stress by up-regulating the Nrf2/HO-1 signalling pathways, and decreased the pro-inflammatory factors by down-regulating TLR4/NF-κB signalling pathways. Furthermore, we validated effects of PGPs on balancing the gut-liver axis by maintaining the integrity of the intestinal epithelial barrier of decreasing intestinal permeability, increasing intestinal tight-junction protein and mucin expression and elevating the abundance of short-chain fatty acids (SCFAs) producers in the intestine by regulating the microbiota composition.