Abstract: Cyanobacterial mats from hyper saline lakes in northern western desert, Egypt, were extracted in seven solvent and their antimicrobial activities against 10 pathogens were examined. The chemical extracts of the cyanobacterial mats exhibited antibacterial activity against 5 out of 10 tested pathogenic bacterial strains at 1 mg mL–1 concentration, whereas the resistant pathogens were highly susceptible, except Pseudomonas aeruginosa, at higher concentration of 5 mg mL–1. A total of 44 chemical compounds were detected by GC-MS. The chemical composition of cyanobacterial mats varied from one lake to the other with highest number of compounds found in Zieton Lake. Twenty five compounds were unique and were present only in extract of particular cyanobacterial mat but absent in the others. All extracts contained a suite of short chain C14-C20 fatty acids, amino acids, alcohols, esters and benzene derivatives. Phytochemical screening of cyanobacterial mats revealed the presence of terpenoids, alkaloids, saponins and glycosides. Lake Zieton is a good source of both terpenoids and glycosides compounds. Petroleum ether and n-hexane are the most effective solvents for isolate active saponins. The results indicated that cyanobacterial mats of northern western desert of Egypt have diver’s chemical and phytochemical compounds that are effective against a wide spectrum of microbes.