The fungal sources of novel metabolites have broadened from saprophytic terrestrial strains to marine habitats and living plants with their endophytes. Specifically, metabolites isolated from species of genus Aspergillus have continually attracted the interest of pharmacologists due to their broad array of biological activities and their structural diversity. Bioassay guided fractionation of the extract of saline culture of marine-derived Aspergillus flavus led to the isolation of eight compounds; kojic acid (1), aflatoxin B1 (2), maculosin1(3), hexahydro-3-(4-hydroxybenzyl)pyrrolo[1,2-a]pyrazine-1,4-dione (4), cyclopiazonic acid (5), cyclopiazonic acid imine (6), aspergillic acid (7) and hydroxyaspergillic acid (8). Structure elucidation of the compounds was based on dereplication using NMR and MS data. A cultivation-based approach was employed to compare the secondary metabolites diversity associated with A. flavus in eight sea water culture media. The type of medium exhibited a significant difference in the yield and the chemistry of compounds responsible for biological activities of the corresponding extract.