Sponges are sessile animals and important filter feeders belonging to the phylum Porifera. These organisms have developed efficient defense mechanisms, harboring bacterial communities capable of producing bioactive compounds. These compounds may aid in antibiotic production research since they were shown to be active against bacteria of medical importance. The current study aimed at the isolation and identification of some sponge-associated bacteria and to evaluate their potential as antimicrobial producers. Five Gram-positive bacterial isolates were isolated from the two sponge species; Ircinia echinata and Amphimedon sp., collected from the Egyptian coast of the Red Sea on Egypt (Hurghada). The 5 bacterial isolates were coded as HA1, HA2, HA3, HA4, and HA5, and identified by 16S rDNA analysis as Bacillus sp., Lysinibacillus boronitolerans, Planomicrobium flavidum, Bacillus safensis, and Bacillus pumilus; respectively. The bacterial isolates were evaluated for their antimicrobial activity as well as multidrug-resistant pathogens. The results revealed that three of the isolates had strong antimicrobial potential towards multidrug-resistant bacteria. Meanwhile, two isolates showed  no vast antimicrobial potential. These findings suggested that the marine bacteria may represent a promising source of antimicrobial agents, as an important strategy for developing alternative therapies for treating infectious diseases caused by multidrug-resistant bacteria.