Urinary tract infections (UTIs) are one of the most frequently acquired infections. Due to the emergence of drug resistance mechanisms in the organisms involved, they are becoming extremely difficult to treat. The emergence of drug resistance due to the production of extended-spectrum beta-lactamases (ESBL) is also very common in UTI nowadays. Medicinal plants Ocmium teniflorum (Tulsi) and Azadirachta indica (Neem) are well-known for their medicinal uses in Unani and Ayurveda medicinal systems. Endophytic actinomycetes confer fitness to the host plant by producing a variety of bioactive metabolites. They are also known to mimic the compounds produced by the plant or produce more potent metabolites due to their exposure to the plant environment. Therefore, the aim of the present study was to compare the antimicrobial activity of endophytic actinomycetes inhabiting tulsi and neem plants with those of the plant extracts against ESBL uropathogens. Preliminary screening displayed 12 endophytes with prominent bioactivity. Interestingly, biological screening of their concentrated broth exhibited excellent inhibitory activity against all ESBL uropathogens i.e. E. coli and Klebsiella pneumoniae. Further minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) also confirmed the endophytic actinomycetes to be producing more potent antibiotics against ESBL producers as compared to the plant extracts. They inhibited the ESBL producers at a concentration of 100mg/ml. Our study indicated that the endophytic actinomycetes inhibiting tulsi and neem plants are possibly producing more bioactive compounds than the plant itself against ESBL producers involved in urinary tract infections.