Tetrapleura tetraptera, widely used in West Africa, is known for its rich phytochemical composition and diverse therapeutic properties. Phenylhydrazine (PHZ) is a well-established hemolytic agent that induces oxidative stress, hematological disturbances, and secondary cardiac alterations. This study evaluated the hematoprotective and cardioprotective effects of the aqueous extract of T. tetraptera in PHZ-induced toxicity in rats. We randomly assigned 20 rats (165 - 195 g) to four groups (n = 5): control, PHZ (150 mg/kg), PHZ plus 200 mg/kg extract, and PHZ plus 400 mg/kg extract. Treatments were administered for 21 days. Hematological parameters were analyzed using an automated hematology analyzer, while cardiac histology was assessed using hematoxylin and eosin staining. Body weight, heart weight, and cardiosomatic index were evaluated. Data were analyzed using one-way ANOVA with Tukey’s post hoc test. Phytochemical analysis revealed the presence of alkaloids, flavonoids, phenolics, glycosides, tannins, and saponins. PHZ administration significantly reduced red blood cell count, hemoglobin concentration, and mean corpuscular hemoglobin concentration, while increasing mean corpuscular volume, red cell distribution width, leukocyte count, and platelet indices. Histological findings showed myocardial fiber compaction and reduced interstitial spaces, indicative of cardiac remodeling. Co-administration of T. tetraptera extract ameliorated these alterations in a dose-dependent manner, with the 400 mg/kg dose showing marked improvement in hematological indices and preservation of myocardial architecture T. tetraptera demonstrated significant haemato-protective and cardioprotective effects against PHZ-induced toxicity, likely mediated through its antioxidant phytoconstituents. These findings support its potential as a natural therapeutic agent in the management of oxidative stress-related hematological and cardiovascular disorders.