Hypertension is an important risk factor for cardiovascular diseases, which are major causes of mortality globally. This study evaluated the  antihypertensive effects of Harungana madagascariensis on sodium fluorideinduced hypertension. Twenty-five rats were randomly divided into five groups (A-E). Group A (control), received normal food and water with no treatment; Groups B to E were exposed to 300 ppm sodium fluoride (NaF). In addition, Group C was treated with 10 mg/kg enalapril, while Groups D and E were treated with 100 mg/kg and 200 mg/kg of H. madagascariensis extract, respectively. The result showed that there was a significant decrease in the systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) of the rats treated with 200 mg/kg of H. madagascariensis compared with rats exposed to NaF alone. Also significant increase was observed in the activities of the enzymatic and non-enzymatic antioxidants in the cardiac and renal tissues of rats treated with 100 mg/kg and 200 mg/kg of H. madagascariensis extract similar to enalapril, compared with rats exposed to NaF alone. However, serum nitric oxide (NO) decreased significantly in rats exposed to NaF alone compared with rats that received 200 mg/kg H. madagascariensis as treatment. Blood urea nitrogen (BUN) and creatinine increased significantly in rats exposed to NaF alone compared with rats that received 200 mg/kg H. madagascariensis as treatment. The histopathology of the cardiac tissue of the rat exposed to NaF alone showed mild hydropic and vacuolar degeneration of cardiomyocytes, while the renal tissue showed foci of markedly flattened tubular epithelial cells and congestion of interstitial blood vessels. The aforementioned lesions were ameliorated in rats treated with 200 mg/kg H. Madagascariensis. In conclusion, H. madagascariensis had potent antihypertensive effect in rats. The effect was probably mediated via the alleviation of oxidative stress in cardiac and renal tissues. Key words: Harungana madagascariensis, Antioxidant activity, Oxidative Stress, Hypotensive effect, Sodium fluoride.