Hyperlipidemia and oxidative stress are risk factors for atherosclerosis. In this study, we investigated the hypolipidemic and anti-lipoprotein oxidation activities of polyphenol-rich extracts from almond hulls using Triton WR-1339 and high-fat diet-induced hyperlipemic mice as experimental models. We demonstrated that the almond hull extract significantly reduced total cholesterol, triglycerides and low-density lipoprotein-related plasma cholesterol (LDL-C) in the two experimental models of hyperlipidemia, but significantly increased high-density lipoprotein-related plasma cholesterol (HDL-C). Another beneficial effect of the extract was its ability to reduce the atherogenic index and LDL-C/HDL-C ratio. However, the extract exhibited effective antiradical activity against 2,2-diphenyl-1-picrylhydrazyl and significantly protected lipoprotein-rich plasma from mice against oxidation induced by copper ion. The extract contains 342.63±3.44 mg/g total phenolics, 144.67±6.83 mg/g tannins, and 20.66±0.92 mg/g flavonoids. These finding indicate that almond hulls contain polar products able to lower plasma lipid concentrations and which might be beneficial for the treatment of hyperlipidemia and prevention of atherosclerosis.