Dyslipidemia and imbalance of electrolytes are among the modifiable risk factors for cardiovascular diseases (CVDs) which cause morbidity and mortality in hypertensive patients. Consumption of fruits and their juices has been shown to be beneficial health wise by lowering risk of coronary artery/cardiovascular diseases, stroke and other degenerative diseases. The lowering effects and protective mechanism of these fruits are probably due to numerous beneficial nutrients and extra-nutrients found in these fruits, such as mono- and poly-unsaturated fatty acids, antioxidant vitamins, secondary plant products, digestive fiber, mineral elements (such as calcium and magnesium), plant proteins and peptides. This preliminary study is aimed at determining the effect of Citrullus lanatus fruit and seed juice on some cardiac enzymes, lipid profile, and electrolytes in normal albino rats. Twenty rats were divided into four groups of five each; a control and three experimental groups. The three experimental groups were given respectively, the doses of 1.7 g, 3.4 g, and 6.8 g per kg of body weight daily for 14 days. Serum Aspartate Aminotransferase (AST), Creatine kinase (CK), Lactate Dehydrogenase (LDH), total cholesterol (TC), triglyceride (TG), high-density lipoproteins (HDL-C), low-density lipoproteins (LDL-C), potassium and sodium were determined. The results showed significant decrease (P < 0.05) in the levels of Creatine kinase between the test groups (3.4 g/kg and 6.8 g/kg), triglycerides and LDL-C between the test groups (1.7 g/kg and 6.8 g/kg) and also sodium between the test groups (1.7 g/kg and the other two 3.4 g/kg and 6.8 g/kg). Also, significant increase (P < 0.05) was observed in LDH levels between the test groups (3.4 g/kg and 6.8 g/kg), triglycerides levels between the control and test groups (1.7 g/kg and 3.4 g/kg), LDL-C levels between the control and test group (1.7 g/kg) and sodium levels between the control and the test group (1.7 g/kg). Serum AST, TC, HDL-C and potassium levels were not affected significantly. The significant decreases in CK, TG, LDL-C, and sodium, suggest that consumption of extract from a blend of seed and pulp of Citrullus lanatus fruits may have cardiovascular disease risk decreasing potential at the doses administered.