Aims: Ethnopharmacological information indicates that the stem bark of Pterocarpus santalinoides is used in traditional medicine to treat many diseases including hypertension. Thus, this study was designed to evaluate the therapeutic effects of the stem bark aqueous extract of Pterocarpus santalinoides (AEPS) in L-NAME-induced hypertensive rats (LNHR). Methodology: Hypertension was induced in normotensive rats by intraperitoneal administration of L-NAME (25 mg/kg/day) for 42 days. Forty-two animals were divided into two main groups: one group of seven rats (group 1) receiving distilled water (10 mL/kg) and another thirty-five rats receiving L-NAME (group 2). After three weeks of treatment, the hypertensive animals (group 2) were divided into five groups of seven rats each. Animals of the first group received distilled water, those of the second group were treated with captopril (20 mg/kg), and the three last groups received the AEPS (50, 100, and 200 mg/kg). These rats were daily treated per os with the above substances for three weeks. At the end of the experimental period (42 days), animals were anesthetized and the blood pressure and heart rate were recorded by invasive method. Afterward, the blood, aorta, and heart of each rat were collected for some biochemical and/or histological examination. Results: L-NAME administration induced hypertension, as associated with left ventricular hypertrophy, dyslipidemia, oxidative stress, hepatic and renal dysfunctions. Aqueous extract administration significantly improved all these metabolic disorders induced by L-NAME. Furthermore, the remodeling of the aortic media after NO deficiency-induced L-NAME has also been improved by Pterocarpus santalinoides aqueous extract. The therapeutic effect of AEPS against L-NAME-induced hypertension could probably be due to its antihypertensive, hypolipidemic, and antioxidant properties. Conclusion: Current results confirmed the empirical use of Pterocarpus santalinoides stem bark for the treatment of hypertension in traditional medicine.