Considering antimicrobial resistance problem, marine microorganisms with the bioactivity against multi-drug resistant (MDR) pathogens have attracted many scientific interests. To address this issue, a total of 21 marine actinomycetes isolated from the Caspian Sea have been screened out. Primary screening via cross-streak method revealed that 3 strains: MN2, MN39, and MN40 produce antimicrobial agents with wide spectrum activity. In the second step, the potent strains were characterized morphologically, and then identified genetically using 16S rRNA analysis. After that, the bioactivity of the ethyl acetate extracts of liquid culture against some MDR bacteria has been studied using disc diffusion method. Finally, the exoenzymatic activity of the strains, and the anti-vibrio activity of the extracts have been evaluated. The nucleotide sequence of the 16S rRNA gene (1.5 kb) showed that the potent strains belong to the genus Streptomyces. The results of disk diffusion method indicated that among the 3 potent isolates, MN39 and MN2 produce biomolecules with antibacterial activity against MDR bacteria specially methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). In addition, potent strains showed remarkable anti-vibrio activity as well as extracellular enzyme production including amylase and protease. The results of this study revealed that the marine actinomycetes isolated from the sediments of Caspian Sea produce biomolecules effective against MDR bacteria, and suggested that these strains deserve to be studied as potential probiotics due to their anti-vibrio activity besides exoenzyme production.