The purpose of this study was to determine the hypolipidemic effects of the glycosaminoglycans (GAGs) extracted from a sea cucumber, Metriatyla scabra. Using DEAE column chromatography, two major peaks containing GAGs were obtained: peak 1 (P-1) contained mainly GAGs (as hexuronic acid and hexosamine), whereas P-2 contained mostly free glycan (as fucose) with little hexuronic acid or hexosamine. Therefore, we used only the P-1 fraction (with molecular weights in the range 200-500 kDa) for evaluation of hypolipidemic effects. The lyophilized GAGs were administered orally to male Wistar rats at 5, 10, 20, and 50 mg/kg body weight for six consecutive weeks, during which the rats were fed ad libitum a basal laboratory diet with or without 1% cholesterol. The results show that the 1% cholesterol diet significantly increased plasma total cholesterol, LDL-cholesterol, and atherogenic index. Cholesterol supplementation also significantly increased hepatic TG, cholesterol, phospholipid, and liver weight. When rats fed the 1% cholesterol diet were supplemented orally with the sea cucumber GAGs, plasma levels of total cholesterol, LDL-cholesterol, and atherogenic index were significantly decreased, while HDL-cholesterol was significantly increased, although these effects of the GAGs were only dose-dependent at doses lower than 20 mg/kg b.w. Similarly, the GAGs significantly prevented the increase (p < 0.05) in hepatic contents of triglyceride, cholesterol, and phospholipid. Thus, the present study demonstrates that the sea cucumber GAGs have the potential of being used for reducing the risk of atherosclerosis and hyperlipoproteinemia.