The phytochemical composition of a plant gives an impression of its medicinal property. Plumbago Zeylanica (Pz) is one of the medicinal plants in sub-Saharan Africa consumed as a supplement for maintaining good health and as an aphrodisiac for enhancing sexual vigor. There is paucity of data on the phytochemical screening and the acute Oral toxicity of root of Plumbago zeylanica harvested in Africa. This study evaluated the bioactive compounds and the acute Oral toxicity of ethanolic root extract of Pz. Phytochemical screening was done using standard and the acute Oral toxicity was conducted and computed using the improved Up-and-Down (UPD) method of Organization for Economic corporation and Development test guideline 425 statistical program which provides a point estimate of LD50. Phytochemical analysis revealed high phenolic and steroid content, a moderate content of flavonoid, terpenoid and alkaloids. Saponin was not detected. The phytochemical composition of ethanolic root extract of Pz suggest a high nutritional and medicinal value, the LD50 was >5000mg/kg body and the smallest usable dose recommended is 100mg/kg body weight.