The acute toxicity profile of Euphorbia taifensis Methanolic-aqueous Extract in rats was investigated in this study. The objectives were to determine its oral median lethal dose (LD50), assess its effects on body weight changes, and evaluate its impact on hematological parameters. The LD50 was determined through oral administration of the extract at a concentration of 2000 mg/kg. No mortality occurred, and no signs of acute toxicity were observed throughout the experimental period. Body weight changes were monitored for 14 days, and no statistically significant differences were observed between the E.taifensis-treated rats and the control rats. The study evaluated the impact of E. taifensis extract on blood parameters. While white blood cell counts remained stable, neutrophils and monocytes increased significantly, and eosinophils decreased. Red blood cell and hemoglobin levels were unaffected, but red cell indices notably changed. Additionally, the extract significantly affected platelet count and volume. In conclusion, Euphorbia taifensis extract showed no acute toxicity at 2000 mg/kg, with no mortality or significant body weight changes observed. Hematological analysis revealed the extract may have diverse effects on blood parameters, warranting further research into its potential therapeutic applications