Twenty-five selected plants belonging to 19 families were collected from different localities of the island Soqotra, dried and extracted with the solvents chloroform, methanol and hot water to yield 80 extracts. The extracts were tested for their antimicrobial activity against several Gram-positive and Gram-negative bacteria and against one yeast species using agar diffusion method. Antibacterial activity was demonstrated especially against Gram-positive bacteria including multiresistant Staphylococcus strains. The greatest activity was exhibited by the methanolic extracts of Boswellia elongata, Boswellia ameero, Buxus hildebrandtii, Commiphora parvifolia, Jatropha unicostata, Kalanchoe farinacea, Pulicaria stephanocarpa, Punica protopunica, Withania adunensis and Withania riebeckii. Only the methanolic extract of Buxus hildebrandtii displayed significant antifungal activity.