Finding natural antimicrobial compounds with minimum side effects on health is important due to increasing numbers of antibiotic–resistant strains. Mangrove plants have extensively been used in medicinal fields. In the present study, four extracts from Avicenna marina and Rhizophora stylosaleaves were prepared using water and different solvents including: ethyl acetate, ethyl ether and ethanol. Antimicrobial activities were tested against some antibiotic–resistant and pathogenic bacterial and fungal species. Ethyl acetate showed the best results as inhibition zones. Leaf extracts of R. stylosa showed inhibition zones ranged from 11–19 mm, while A. marina showed 11–20 mm, against most of the tested microorganisms. Results showed also that, the greatest effect was towards Escherichia coli and the lowest was against Candida albicans. The qualitative phytochemical analysis revealed that, extracts of mature leaves contained tanines, flavonoids, terpenoids, alkaloids as well as steroids, phenolic flavonoids and Cardiac glycosides. The present study reported the great effect of A. marina and R. stylosa extracts against some of most important human, plant and animal pathogens.