Marine macro algae are useful to mankind as food, biofertilizer, and source of bioactive compounds such as agar-agar, alginates, and carrageenan. The aim of this study was to explore the phytochemicals, and the antibacterial activity of the marine alga Sargassum polycystem. The marine alga was subjected to ethanolic and methanolic extractions. The preliminary screening for phytochemicals showed the presence of tannins, polyphenols, saponins, cardiac glycosides, and quinones. The GC-MS analysis revealed the presence of totally 16 secondary metabolites: 8 different compounds for each solvent extraction. Among these bioactive compounds, 3 compounds (1, 2 benzenedicarboxylic-dibutylester and 13, docosenamide of ethanolic extract, and 3, 5-diaminodeoxymethoxy of methanolic extract, showed the binding affinity and ability to react with exotoxin-A of Pseudomonas aeruginosa, a common pathogenic bacterium of fishes and prawns. The in vitro antibacterial assays revealed that both ethanolic and methanolic extracts of S. polycystem possessed the ability to inhibit the growth of P. aeruginosa. Therefore, aquaculture medicine could be prepared with S. polycystem.