Buruli ulcer is the third most prevalent mycobacteriosis, after tuberculosis and leprosy [1]. The currently recommended combination of Rifampicin-Streptomycin is challenged by side effects and poor compliance, which leads to reliance on local herbal remedies [2,3]. The objective of this study was to investigate the antimycobacterial properties and toxicity of selected medicinal plants. Sixty-five extracts from 27 plant species were screened against Mycobacterium ulcerans and Mycobacterium smegmatis, using the Resazurin Microtiter Assay (REMA). The cytotoxicity of promising extracts was assayed on normal Chang liver cells by MTT assay. Twenty five extracts showed activity with minimal inhibitory concentration (MIC) values ranging from 15.31 µg/mL to 250 µg/mL against M. smegmatis while 17 showed activity against M. ulcerans with MIC values ranging from 125 µg/mL to 250 µg/mL. In most of the cases, plant extracts with antimycobacterial activity showed no cytotoxicity on normal human liver cells. Exception were Carica papaya, Cleistopholis patens, and Polyalthia suaveolens with 50% cell cytotoxic concentrations (CC₅₀) ranging from 3.83 to 223 µg/mL. Qualitative preliminary phytochemical analysis performed on the promising the extracts revealed phytoconstituents that might be responsible for the observed antimycobacterial activity such as phenols, tannins, flavonoids, saponines, alkaloids, anthraquinones, glycosides, and triterpenes. These preliminary results support the use of some West African plants in the treatment of Buruli ulcer. As well, the chemical profile of active extracts will provide guidance for further investigations in pharmacological properties of active ingredients.