Cardiovascular disease (CVD) is the most frequent cause of death in Western industrialized nations. The probability of CVD is directly related to blood cholesterol levels, among several other factors such as hypertension, smoking, malnutrition, obesity, and stress. It is well known that changes in lifestyle, including physical activity and dietary changes such as reduction in the consumption of saturated fat, can reduce blood cholesterol levels. In such cases, dietary soy-protein supplementation, for which cholesterol-lowering properties have been shown in many clinical studies, is useful to postpone the need for cholesterol-lowering medication such as statins. In this review, we will summarize numerous clinical studies conducted with soy-protein supplementation in various formulations that exhibit clear low-density lipoprotein (LDL) cholesterol-lowering effects. To get more homogeneous results, we summarized only clinical studies conducted with soy-protein supplements containing the same isolated soy proteins, cotyledon fibers, and phospholipids: Nutri 5, Abalon, and Abacor (all by Nutri Pharma ASA, Norway), which have shown clear cholesterol-lowering efficacy. Furthermore, these studies demonstrate that homocysteine, an independent CVD risk factor, is also reduced |by soy-protein supplementation. Differences between studies showing clear LDL-lowering effects for soy protein and those that do not are discussed, as well as possible mechanisms of action for soy-protein supplementation on blood cholesterol levels.