In order to obtain homogeneous Sanghuangporus vaninii polysaccharides with antioxidant and anti-inflammatory activities, a response surface method (RSM) was used to compare the polysaccharide extraction rate of hot water extraction and ultrasonic-assisted extraction from Sanghuangporus vaninii. The optimal conditions for ultrasonic-assisted extraction were determined as follows: an extraction temperature of 60 °C, an extraction time of 60 min, a solid–liquid ratio of 40 g/mL, and an ultrasonic power of 70 W. An SVP (Sanghuangporus vaninii polysaccharides) extraction rate of 1.41% was achieved. Five homogeneous monosaccharides were obtained by gradient ethanol precipitation with diethylaminoethyl–cellulose (DEAE) and SephadexG-100 separation and purification. The five polysaccharides were characterized by high performance liquid chromatography, the ultraviolet spectrum, the Fourier transform infrared spectrum, TG (thermogravimetric analysis), the Zeta potential, and SEM (scanning electron microscopy). The five polysaccharides had certain levels of antioxidant activity in vitro. In addition, we the investigated the anti-inflammatory effects of polysaccharides derived from Sanghuangporus vaninii on lipopolysaccharide (LPS)-induced RAW 264.7 cells and Kupffer cells. Further, we found that SVP-60 significantly inhibited the levels of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-induced RAW 264.7 cells and promoted the level of the anti-inflammatory cytokine IL-10 in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Our study provides theoretical support for the potential application of Sanghuangporus vaninii in the field of antioxidant and anti-inflammatory activities in vitro.