This study examines the acute toxicity of the aqueous extract of Jatropha tanjorensis leaf in mice and its effects on lipid profiles and haematological parameters in male Wistar rats. Acute toxicity assessment showed that graded doses of the extract up to 6000 mg/kg did not cause mortality. However, at 7000 mg/kg, a 33.33% mortality rate was observed, and 100% mortality occurred at 10,000 mg/kg. The extract caused a gradual decrease in total cholesterol (TC) at 400 mg/kg and 800 mg/kg. High-density lipoprotein cholesterol (HDL-C) increased in a dose-dependent manner. Low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein cholesterol (VLDL-C) levels decreased. Atherogenic and coronary risk indices were significantly reduced (p<0.05) at 400 and 800 mg/kg, indicating improved cardiovascular health. Haematological analysis showed increased red blood cell (RBC) count and packed cell volume (PCV). Haemoglobin levels also increased significantly. Total white blood cell (TWBC) count increased with lower doses but decreased (p˂0.05) at 800 mg/kg. Mean corpuscular volume (MCV) decreased, while mean corpuscular haemoglobin concentration (MCHC) increased. Differential WBC counts showed increased (p˂0.05) neutrophils and variable lymphocyte percentages, with no detectable basophils. These results suggest that the extract has notable effects on lipid and haematological parameters, with significant toxicity at high doses, warranting further investigation into its safety and therapeutic potential.