, native to the Arabian Peninsula, is traditionally used to cure skin infections. The objective is to screen the phytochemical content and antimicrobial activity of aqueous, methanol and 80% methanol extracts of aerial parts of R. epapposum. The phytochemical screening of aqueous, methanolic, and 80% methanol extracts of R. epapposum was conducted using gas chromatographymass spectrometry. The antimicrobial activities of the extracts were assessed by well diffusion and microdilution methods. Qualitative phytochemical analysis revealed the presence of 2-methoxy-4-vinylphenol in all three extracts, whereas ethanol, 2-methoxy-, acetate; n-hexadecanoic acid; and 2,3-butanediol are present in higher amount exclusively in the methanol, 80% methanol and aqueous extracts of the aerial parts of R. epapposum, respectively. The highest antibacterial activity was shown by the aqueous extract S. aureus, P. aeruginosa, E. cloacae, and K. pneumoniae, methanolic extract against S. aureus, methicillin-resistant S. aureus, and E. coli, and 80% methanol extract against S. epidermidis, and S. paucimobilis. Interestingly, 80% methanol extracts showed the highest antifungal activity against C. albicans, C. guillermondii, C. vaginalis, C. utilis, and C. tropicalis. The aerial parts of R. epapposum showed broad-spread antimicrobial activity against bacteria and fungi. Especially, the 80% methanol extract showed potent antifungal activity against all the tested fungal strains.