Dietary proteins affect blood cholesterol concentrations and antioxidant status, which are related to several diseases, including cardiovascular disease. The present study attempts to investigate the potential of Boops boops proteins (Bb-NHP) and its hydrolysate (Bb-HP) in the prevention of hypercholesterolemia and oxidative stress in rats fed a high cholesterol diet (HCD). After four weeks' treatment, serum lipid profiles (total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol), the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the level of malonaldehyde (MDA) and the activities of antioxidant enzymes [catalase (CAT) and glutathione peroxidase (GPx)] in liver were determined. Compared with those fed a standard diet, high cholesterol diet induced dyslipidemia, oxidative stress, and aortic structure alterations. Interestingly, supplementing the HCD with Boops boops proteins attenuated these anomalies in a dose-dependent manner. These observations suggested that B. boops proteins might provide health benefits by helping to reduce the deleterious effects of increased intake of cholesterol that characterize modern diets.