Ocmium teniflorum (Local name: Tulsi, Family: Lamiaceae) is a plant well known for its medicinal uses in unani and ayuveda medicine. It is called the ‘queen of herbs’ for its antimicrobial, antiinflammatory, hypotensive, hypoglycemic antipyretic and analgesic activities. Azadirachta indica (Local name: Neem, Family: Meliaceae) is a medicinal plant best known for its antimicrobial, antiinflammatory, anticancer and antiviral activities. It is a fact that the individual exudates of each plant attract a specific species of microbes and induce them to produce possible novel compounds under the influence of the plant environment. With this idea in mind, we investigated the antimicrobial activity of endophytic actinomycetes inhabiting tulsi and neem plants. The preliminary screening was done using agar plug method and it displayed 12 isolates with prominent bioactivity. Further biological screening of their active metabolites showed that the compounds were most active against Salmonella enteritidis, Campylobacter jejuni and Proteus mirabilis. The thin layer chromatography (TLC) and high performance liquid chromatography-UV (HPLC-UV) displayed UV absorbing polar and non polar compounds. Our study reveals tulsi and neem plant microenvironment as an unexplored niche harboring endophytes that are prominently bioactive against multidrug resistant (MDR) poultry and human pathogens.