OBJECTIVE Clerodendrum myricoides is a Kenyan herbal plant used in the management of respiratory diseases. In the current study, we investigated in vitro antimicrobial activity, cytotoxicity, and phytochemical screening of C. myricoides. METHODS Antimicrobial activities of C. myricoides organic fractions against array of microorganisms including: (i) Mycobacterium tuberculosis (MTB) H37Rv, (ii) Staphylococcus aureus, (iii) Klebsiella pneumoniae, (iv) Escherichia coli, (v) Candida albicans, (vi) Pseudomonas aeruginosa, (vii) Cryptococcus neoformans, (viii) Salmonella typhi, (ix) Shigella sonnei, and (x) Methicillin-resistant S. aureus (MRSA) were investigated by disc diffusion and microdilution techniques. Antituberculous activity was investigated using BACTEC MGIT 960 system while cytotoxicity was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on HEp-2 cells. Finally, phytochemicals were screened using standard procedures. RESULTS Methanolic fractions exhibited a broad spectrum activity inhibiting 75% of test pathogens. It had the highest activity with minimal inhibition concentration (MIC) values of ≤62.5 µg/ml recorded against 62.5% tested microbes. It yielded the highest zone of inhibition of 20.3 mm (S. aureus), lowest MIC of <12.5 µg/ml (MTB), and the lowest minimal bactericidal concentration of 62.5 µg/ml (C. albicans), within the acceptable toxicity limit (CC50 >90 µg/ml). The phytochemicals largely believed to be responsible for the observed activity included: Alkaloid, phenols, anthraquinones, terpenoids, and flavonoids. CONCLUSIONS Methanolic fraction had remarkable activity against MRSA, S. aureus, E. coli, S. sonnei, C. albicans, and MTB, which are of public health concerns due to drug resistance and as sources of community and nosocomial infections. To the best of our knowledge, this is the first report exploring the antituberculous activity of C. myricoides and thence a major output in search of novel, safe drug leads to mitigate the global tuberculosis threat.