Three species of sponge and one species of sea cucumber representative to marine invertebrates were collected from the Red Sea, Hurghada, Egypt. They were identified based on general morphological and anatomical features as Cinachyrellaarabica, Ciocalyptapenicillus, Axinellaverrucosa, and Holothuria  atra. Their antibacterial and antifungal activities in crude extracts were investigated and data revealed that the positive values were recorded in the range of 8 to 20 mm by the ethyl acetate crude extract obtained from C. arabica. E. coli was the most affected bacterium followed by S. typhimurium that was 18 mm by the ethyl acetate crude extract obtained from A. verrucosa. Also, the fungal suppression % was in the range of10-100% by all kinds of sponge crude extracts.  However, the ethanolic extract of C. arabica and ethyl acetate extract of C. penicillus had the highest suppression %, followed by the ethanolic extract of C.penicillus as of 90%. Likewise, the highest activity was detected by H. atra methanolic crude extract against A. hydrophila, followed by the same extract against S. aureus (14 mm). Only P. notatum was the fungus that affected by both ethanolic and methanolic extractswith 20% suppression. On the other side, results of GC-MS/MS of crude extract observed the presence of several bioactive constituents, most of which had antimicrobial activities.