Brachychiton rupestris and Brachychiton luridum are deciduous trees belonging to family Malvaceae. Several members of the genus Brachychiton and its related genus, Sterculia, are used in folk medicine for the treatment of infections. Herein, we investigated the antimicrobial activity of the total extracts, n-hexane, dichloromethane as well as the ethyl acetate fractions of the leaves of both species using agar well diffusion method in an effort to better consolidate the scientific basis for their traditional uses. The study was carried out against two Gram-positive and two Gram-negative bacteria together with two fungi. The extracts and fractions showed mean inhibition zones diameter in the range of 10.97-14.98 mm with minimum inhibitory concentration values ranging between 39.06 and 625 µg/mL against the susceptible bacteria and fungi. The ethyl acetate fraction of B. luridum exhibited notable activity against Staphylococcus aureus while the total extract showed moderate activity against Salmonella typhi. Regarding B. rupestris, the total extract, n-hexane and ethyl acetate fractions showed moderate activity against Escherichia coli, Candida albicans, and Salmonella typhi, respectively. Other extracts and fractions showed weak or no activity against the tested microorganisms. Qualitative phytochemical screening of both plants was performed to preliminary unveil the classes of secondary metabolites present in the leaves. The results indicated the existence of flavonoids, tannins, sterols, triterpenes, carbohydrates and/or glycosides in both plants.