The aim of the present study was to evaluate the antagonistic activity of marine Streptomyces sp. VITBRK1 against Methicillin resistance Staphylococcus aures (MRSA) and vancomycin-resistant Enterococci (VRE). Drug resistance by Bacterial pathogens do exhibit significant tolerance to standard antimicrobials during infections and drug resistance currently a growing problem worldwide. A total of 137 actinomycetes isolated from marine sediments were screened for antibacterial activity against ATCC MRSA and VRE strains. Twenty two isolates exhibited antagonistic activity against standard ATCC strains. The potential isolate which showed activity against drug resistant pathogens was characterized by molecular taxonomic approach and identified as Streptomyces and designated as Streptomyces sp. VITBRK1. The isolate showed significant antibacterial activity against MRSA strains with the zone of inhibition of 24 mm against Staphylococcus aureus (ATCC 29213), 21 mm against Staphylococcus aureus (25923), 21 mm against Staphylococcus aureus (700699) and 13 mm against Staphylococcus aureus (U2A 2150). It also showed antibacterial activity against VRE strains, 25 mm zone of inhibition against Enterococcus faecalis (ATCC 29212), 19 mm against Enterococcus faecium (BM4107), 24 mm against Enterococcus faecium (BM4147) and 23 mm against VRE clinical isolate. HPLC-DAD analysis showed the presence of indolo compounds along with two unknown metabolites. The observed activity of Streptomyces sp. VITBRK1 may be due to the presence of compounds in the isolate. The results of this study suggest that secondary metabolites produced by Streptomyces sp. VITBRK1 could be used against MRSA and VRE strains.