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Lannea schimperi and Searsia longipes are plants species under family Anacardiaceae. These plants have been utilized for years in traditional settings for management of an array of disease conditions; however, there is limited information about their safety (toxicity level). The aim of the current study was to evaluate the acute toxicity, cytotoxicity and phytochemical compounds of extracts from the aforementioned plants. Acute toxicity was performed in vivo on Swiss albino mice. Cytotoxicity was done in vitro on brine shrimp larvae and plants were qualitatively screened for five major groups of compounds. Both extracts exhibited good margin of safety on swiss albino mice with LD50 (Lethal dose 50) above 2000 mg/kg body weight. Lannea schimperi and Searsia longipes expressed significant cytotoxicity on brine shrimp larvae with IC50 (Inhibitory concentration 50) of 150.0478 mg/ml and 280.7875 mg/ml respectively. Phytochemical screenings of both extracts have revealed presence of flavonoids, saponnins, tannins and glycosides. The study confirmed the previous reports on the acute toxicity of Lannea schimperi and Searsia longipes, as well as cytotoxicity of Lannea schimperi and for the first time reports the cytotoxicity and phytochemical compounds of Searsia longipes.