The structure, antioxidant and anti-hyperlipidemic activities of polysaccharides from Nitraria retusa fruits (named as NRFP) were investigated. The NRFP fraction, with a molecular weight of 66.5 kDa, was composed of a β-(1 → 3)-glucan, containing neutral sugars (69.1%) but also uronic acids up to 23.1% due to pectin structure. The monosaccharide composition highlighted a polymer composed of glucose (41.4%), galacturonic acid (30.5%), galactose (12.6%), arabinose (11.8%) and rhamnose (3.70%). In the antioxidant assays, NRFP exhibited effective total antioxidant capacity (IC50 = 7.82 mg/ml), scavenging activities on DPPH radical (IC50 = 0.87 mg/ml) and hydrogen peroxide (IC50 = 2.03 mg/ml). In addition, NRFP proved protective effects on H2O2 induced hemolysis (IC50 = 66.2 μg/ml). In vivo NRFP reduced the hyperlipidemia, hepatotoxicity, cardiovascular and coronary diseases induced by Triton X-100.