In this study, the bioactive secondary metabolites obtained from thirteen marine derived fungi were tested against seven pathogens. The reported fungi were isolated from water and sediment samples collected from the Mediterranean Sea at Egyptian coasts. Taxonomically, the fungal isolates were morphologically identified, and classified into five genera: Penicillium (33%), Aspergillus (33%), Fusarium (7%), Acremonium (7%) and yeast (13%). The strains were cultivated preliminary on broth media, and the antimicrobial activities of their supernatants were investigated. The most promising five fungal isolates (Nr.8, 9, 12, 13 and 15) were subsequently cultivated on rice-solid state medium, re-visualizing their antimicrobial activity. From the antimicrobial activity test, the phytochemical profiling of the most interesting isolates (Nr.8 and 13) were analyzed based on GC-MS, and their bioactive secondary metabolites were tentatively identified, revealing the presence of twenty-four and twenty-eight compounds belonging to diverse structural categories, respectively. Furthermore, the last two strains were applied to different agricultural waste as solid-state media; their antimicrobial activities were studied comparatively, and the obtained bioactive secondary metabolites were tentatively assigned as well using GC-MS analysis. We target the selection of the most promising strains for production of auspicious bioactive secondary metabolites, representing as drug leads, for forthcoming full studies