Cancer and infectious diseases are notoriously known as deleterious health threats for the world, especially in the developing countries. The aim of the present study was to evaluate the cytotoxicity and antimicrobial activities of the methanolic extracts of  the soft corals Nephthea elatensis, Heteroxenia fuscescens, Ellisella juncea, Dendronephthya mollis, and Sinularia hirta, that are native to the Red Sea in Egypt. The cytotoxicity assay was carried out by the enzymatic reduction of 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay against lung adenocarcinoma cell line (A549). Moreover, the antimicrobial activity was carried out against 11 human pathogenic bacterial and fungal strains using well-cut diffusion technique, while the Minimum Inhibitory Concentrations (MICs) were determined by microdilution method. Nephthea elatensis showed potent cytotoxicity [half maximal inhibitory concentration (IC₅₀) 11.9 ± 1.2 µg/mL]. Also, it exhibited a potent antibacterial activity against Staphylococcus aureus(MIC 1.0 µg/mL). Sinularia hirta exhibited significant antimicrobial activities against Salmonella typhimurium and S. aureus (MIC 5.0 and 10.0 µg/mL, respectively). The results recommended N. elatensis and S. hirta as promising sources for new anticancer and antibiotic natural candidates.