Encouraged by new drug developments, the present research was investigated on extracts of Red Sea marine resources all from Egypt. Extracts from three sponges namely Spheciospongia vagabunda (SAA-14), Negombata corticata (SAA-8) and Negombata magnifica (SAA-64) in addition to two soft corals Sarcophyton glaucum (SAA-33) and Sarcophyton auritum (SAA-43) were found to display high potential against HepG2 (liver cancer cell line) and MCF-7 (breast cancer cell line). Cytotoxic potential activities of these five extracts were measured by the Sulpho-Rhodamine-B (SRB) assay. The anticancer activity of SAA-8, SAA-14,SAA-33, SAA-43 and SAA-64 was significantly enhanced in the liver cancer cell line with the values ranged from16.3 to 19.3μg/ml and in the breast cancer cell line with concentrations of 24.7, 19.7, 18.7,21.1and 25.8μg/ml, respectively compared to doxorubicin as positive control. Negom batacorticataand Sarcophyton auritum based extracts exhibited promising antifungal activity against fungi of genus Candida, Cryptococcus and Aspergillus, moreover, the five extracts revealed antiprotozoal and antimicrobial activity after in vitro assays. Also Negombata corticata has good antituberculosis, antimalarial and antilieshmanial potentials.