In the present work, we investigated the anti-hyperlipidemic, antioxidant and organic protection effects of acidic-extractable Dictyophora indusiata polysaccharides (Ac-DPS) on hyperlipidemic mice induced by high-fat emulsion. The results demonstrated that Ac-DPS had impressive abilities to mitigate oxidative stress by increasing the activities of antioxidant enzyme and reducing the contents of lipid peroxide. Moreover, lipid levels in serum were returned to normal status. Besides, Ac-DPS exhibited potential hepatic and renal protection effects reflected by decreasing serum enzyme activities, lowering TBIL, UREA and CREA levels and increasing ALB content. At the same time, histopathological observations proved protective effects of Ac-DPS on organs. Subsequently, the physical properties of polysaccharide were also investigated by HPGPC and FT-IR. The above consequences confirmed the important role of Ac-DPS as a functional food and natural medicine in the fight against oxidative stress and the prevention of hyperlipidemia.