Hypertension and dyslipidemia are major causes of cardiovascular disease. Medicinal plants continue to be widely used as therapeutic options for the management of cardiovascular diseases. Santolina africana is a medicinal and aromatic plant of the Asteraceae family, a plant family widely recognized for its beneficial pharmacological effects, particularly in managing cardiovascular diseases. This study aimed to evaluate the antihypertensive, vasorelaxant and antidyslipidemic properties of the aqueous extract of S. africana in animal models of hypertension and dyslipidemia. Normotensive and L-NAME-induced hypertensive rats were orally administered the aqueous extract of S. africana (SAAE) at the doses of 100 and 200 mg/kg and systolic, diastolic and mean blood pressure were measured. The vasorelaxant activity of SAAE and underlying mechanism were evaluated on isolated aortic rings with and without endothelium. Additionally, the antidyslipidemic effect of SAAE (250 and 500 mg/kg) was assessed in Triton WR-1339 induced hyperlipidemic model in rats. Results showed a significant, dose-dependent reduction in blood pressure values in hypertensive rats following SAAE administration. The vasorelaxant effect appeared to be endothelium-dependent and likely mediated by nitric oxide pathway. Furthermore, in Triton WR-1339-induced hyperlipidemic rats, the SAAE significantly lowered plasma levels of total cholesterol, triglycerides and LDL-cholesterol. These findings suggest that S. africana possesses significant antihypertensive, vasorelaxant and antidyslipidemic properties, highlighting its potential as a promising natural therapeutic agent for managing cardiovascular and metabolic disorders.