To investigate the effect of solid-state co-fermentation on the structural characteristics and bioactivities of polysaccharides in the medicinal residues of Gastrodia Ganoderma (RGG), two kinds of polysaccharides were isolated and purified from unfermented RGG and fermented RGG, named RP and FRP, respectively. The results showed that molecular weight of FRP decreased than RP and its monosaccharide composition changed significantly. RP was mainly composed of Glucose (66.46%) and Galactose (22.83%) while the main monosaccharide components of FRP was galacturonic acid (65.67%). Fermentation caused the surface morphology of FRP to become fragmented and loose, and increased its in vitro antioxidant activity. Both RP and FRP could repair cell damage, reduce the secretion of reactive oxygen species, and protect RAW 264.7 cells from LPS-induced inflammation. Molecular docking results indicated that monosaccharide structures in FRP had stronger binding energy for inflammatory markers. This study may provide theoretical reference for the high-value utilization of Chinese herbal residues.