The objective of this current study was to investigate the possible hyperlipidemic and antioxidative effects of Cystoseira crinita sulfated polysaccharide (CCSP) in rats fed with a high-fat diet, exhibited an inhibitory activity on pancreatic lipase in vitro. In vivo administration of this extract to HFD-rats lowered body weight and potentially inhibited key enzymes of lipid metabolism and absorption as lipase activity in both plasma and small intestine, which led to a notable decrease of blood LDL- cholesterol (LDL-Ch) and triglycerides (TG) levels, and an increase in HDL-cholesterol (HDL-Ch) levels in HFD-rats. CCSP was also observed to protect the liver-kidney functions efficiently, by decreasing of aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH) and Creatine phosphokinase (CPK) activities and creatinine, albumin, T-bilirubin, uric acid, and urea rates in plasma. The histological analysis of liver and kidney tissues further established the positive effect of CCSP.