The objective of this current research is to investigate the antibacterial properties of crude extracts derived from various soft coral species Specimens were collected off the coast of Hurghada city in Egypt's Red Sea region. The antimicrobial activity of Sinularia leptoclados, Sarcophyton ehrenbergi, Nephthya molle, and Dendronephthya hemprichi was evaluated against several harmful microorganisms. The well-cut diffusion technique was employed to ascertain the level of activity. The determination of minimal inhibitory concentrations (MIC) and minimal bacterial concentration (MBC) was conducted using the dilution method. These concentrations were assessed against Enterococcus faecalis ATCC 29212, Pseudomonas aeruginosa ATCC 9027, Aeromonas hydrophila ATCC 13037, and Staphylococcus aureus ATCC6538. The antibacterial potential of the crude extract obtained from a mixture of methanol/dichloromethane was 10.0 for S. leptoclados and ranged from 8.0 ± 0.58 to 14.0 ± 0.65 for S. ehrenbergi, and 10.0 ± 0.46 to 24.0 ± 0.68 for D. hemprichi. The D. hemprichi extract showed the highest antimicrobial activity which was carried out through MIC and MBC testing. Additionally, a partial characterization of these substances was conducted utilizing (GC-MS). The findings indicated the presence of varied bioactive substances, however, cis-vaccenic acid was considered the major compound in this species. Our findings revealed the potent antibacterial of Dendronephthya hemprichi compared to the other species.