The polysaccharides of Acanthophora spicifera and Cystoseira trinode were isolated and their components identified using different chemical and spectral techniques. Their effects were evaluated for the first time on hyperlipidemic rats. Atorvastatin Ca (Lipitor®) was used as a reference drug. Results revealed that the polysaccharides isolated were of sulfate type. Acanthophora spicifera lowered the level of total serum lipids, total cholesterol (TC), triglycerides (TG) and low-density lipoproteins (LDL-C) by 48%, 49.6%, 63% and 80.6% respectively. High-density lipoproteins (HDL-C) level was elevated by 1.14 fold. For Cystoseira trinodetotal lipids, TC, TG and LDL-C were decreased by 25.5%, 49%, 51% and 91% respectively. The level of HDL-C was elevated by 1.5 fold in comparison with the hyperlipidemic rats. The histopathological results proved the ameliorated effect after using the isolated polysaccharides of both algae. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities were decreased in hypercholesterolemic groups by values of 63%, 34% and 45%, respectively when treated with A. spicifera extract. The treatment with C. trinode extract and Atorvastatin exhibited a noticeable amelioration in activity with hypercholesterolemic groups as compared to their corresponding controls.