MEDICINAL plants endophytes are a promising trend to meet the increasing threat of drug-resistant strains of human pathogens. Mangrove plants (Avicennia marina) have been used in folklore medicines where extracts from mangrove species have proven inhibitory activity against human, animal and plant pathogens. This study focuses particularly on testing the antimicrobial activity of mangrove endophytic fungi isolated from South Safaga and Wadi Abu Hamrah mangrove along the Red Sea against different human pathogens. A total of 35 endophytic fungi were isolated from mangroves leaves at two study areas and were identified. Crude extracts of the endophytic isolated fungi were screened for their antimicrobial activity using a well diffusion method against the following pathogenic microorganisms; S. aureus, S. pyogenes, P. vulgaris, K. pneumoniae, B. subtilus, C. albicans, P. chrysogenum and A.niger. The most effective extracts which exhibited significant activity against most of the tested pathogens were from A. aculeatus, A. niger, A. terreus, E. amstelodami, E. rostratum and M. racemosus.