Bacterial ailment remains a serious health problem due to its development of resistance to available antibiotics and created the need for replacement. In Ethiopia, the plant Croton macrostachyus are used as a traditional medicine for infectious diseases, but reports on its possible bactericidal activity is deficient, therefore the present study aimed at evaluating the in vitroantibacterial activity of different extracts of C. macrostachyus leaves against six human pathogens of Moraxella catarrhalis, Streptococcus pyogenes, Pseudomonas aeruginosa, Escherichia coli, Streptococcus pneumonia and Neisseria meningitides. The methanol extract was the best in terms of zone of inhibition as exhibited maximum of 12.3 mm diameter followed by chloroform (9.6 mm) and ethanol (7 mm) and clearly indicated that unique bactericidal activity. However, its efficacy will be evaluated in future. The present results give scientific evidence and support the traditional use of C. macrostachyus as a source for antibacterials eventually for unearthing new drugs.