Methods and compositions containing a berberine compound or berberine related or derivative compound are provided for the prevention and treatment of hyperlipidemia, elevated cholesterol, and/or cardiovascular disease in mammalian subjects. The methods and compositions of the invention are effective for prevention and treatment of atherosclerosis, coronary artery disease, angina pectoris, carotid artery disease, stroke, cerebral arteriosclerosis, high blood pressure, myocardial infarction, cerebral infarction, restenosis following balloon angioplasty, intermittent claudication, dyslipidemia post-prandial lipidemia or xanthoma. Additional compositions and methods are provided which employ a berberine compound or berberine related or derivative compound in combination with a second anti-hyperlipidemia agent, or a different therapeutic agent to yield more effective treatment tools against hyperlipidemia and/or cardiovascular disease, and/or dual activity therapeutic methods and formulations useful to prevent or reduce hyperlipidemia and one or more causal or related symptoms or conditions associated with hyperlipidemia in mammalian subjects.