Abutilon fruticosum Guill. & Perr. (Family Malvaceae) is distributed throughout a number of arid and semi-arid regions and has been used in traditional and folk medicine. The current study was conducted to estimate the phytochemical profiling and antimicrobial activity of Abutilon fruticosum Guill. & Perr. growing in Gebel Elba, Egypt against some respiratory tract infections isolates (Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter cloacae, and Acinetobacter baumannii; Gram-positive bacteria: Staphylococcus aureus, Streptococcus epidermidis, and Enterococcus faecalis; and yeast: Candida tropicalis). Phytoconstituents determination of Abutilon fruticosum was carried out using the high resolution ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/qTOF-MS/ MS); which yielded the determination of thirty constituents including phenolic acids, alkaloids and the majority of flavonoids. Abutilon fruticosum extracts were tested for their in vitro antimicrobial activity using the disc diffusion method. Plant extracts exhibited potent antimicrobial activity against the tested isolates. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the most suitable successive fractions were determined. Butanol fraction showed the lowest MIC (25 mg/ ml) against all the tested organisms. While; ethyl acetate fraction exhibited the lowest MIC (12.5 mg/ ml) against Klebsiella pneumoniae. Abutilon fruticosum Guill. & Perr. extracts are enriched in phytoconstituents which are likely attributed to their potential antimicrobial activity.