Background: Cardiovascular disease is a widespread public health problem and hypertension is one of the major risk factors of it. Tridax procumbens leaf extract is traditionally used in the treatment of hypertension. This study evaluates the effects of T. procumbens extract (TPE) on blood biochemical parameters of N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. Materials and Methods: Rats were divided randomly into four different treatment groups. Group I received 0.9% NaCl (control), Group II, III, and IV were given a nitric oxide synthase inhibitor (L-NAME) 40 mg/kg/day, orally for 6 weeks to induce hypertension. Groups III and IV were further treated with TPE (100 and 200 mg/kg/day), respectively, in the past 3 weeks of 6 weeks. Blood pressure, morphological variables, histopathology, plasma lipids, lipoproteins, cholesterol levels, hepatic enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and other parameters were analyzed. Results: TPE markedly inhibited the sustenance of L-NAME-induced hypertension. This effect was accompanied by a partial or full amelioration of most of the adverse effects induced by L-NAME, such as: (1) Increases in blood pressure, organs weight indices; (2) hyperlipidemia; (3) increased plasma activity of glutamic-pyruvic transaminase (ALT) and AST; and (4) liver and cardiac histological lesions. Conclusions: This study provides evidence about the antihypertensive effects and end-organ protection of TPE in animal model of hypertension. These effects may be due to one or more constitution in this extract.