Streptomyce sp. NMF76 was isolated from mangrove sediment at the Egyptian Red Sea coast by serial dilution method and identified based on morphological and biochemical properties as well as 16s rDNA sequence analysis. The culturing parameters maximizing the antimicrobial activity and the MIC values for the tested pathogens were determined. The ethyl acetate extract was analyzed by GC-MS. Morphological and biochemical characteristics and 16s rDNA sequence analysis affiliated the strain to the Streptomyces genus with accession number, MT0199162. It exhibited the maximum antimicrobial activity when cultured in ISP5 medium containing 3% NaCl and incubated at 30 ᵒC for 14 days with glycerol and L-asparagine as carbon and nitrogen sources, respectively. The strain exhibited antimicrobial activity against Vibrio damsela, S. aureus, E. fecalis and C. albicans and the MIC values were 285,400, 461 and 545 µg/mL, respectively. GC-MS analysis of the extract revealed the presence of Benzene, 1,2,4-trimethyl (21.47 %), 2H-Pyran-3-ol,tetrahydro-2,2,6-trimethyl-6-(4-methyl-3-cyclohexen-1-yl)-, [2S- [2à, 5á (R*) ] ]- (18.35 %) , Benzene, 1-ethyl-3-methyl- (15.76 %), and undecane (9.96 %) as major components. Further studies are required to purify and elucidate the structure of the antimicrobial agent.