An easy and rapid microwave-assisted green synthesis of silver nanoparticles (AgNPs) was carried out using aqueous bark extract of arjuna and their antibacterial and anti-biofilm potential was investigated. In the field of medicine, nanomedicines are gaining importance throughout the world for the treatment of different diseases. The AgNPs were characterized by various techniques. The FTIR data revealed the presence of plant organic constituents and metabolites bound to TA-AgNPs, which contributes for their stability. To elucidate the antibacterial efficacy and biofilm inhibition of Ta-AgNps against multidrug-resistant. Pathogenic E. coli harbouring the ESBLs. Treatment of TA-AgNps inhibited the growth of human pathogenic (both gram positive and gram negative) bacterial strains including Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Salmonella typhimurium (ATCC 14028), Proteus mirabilis (ATCC 35659), Acinetobacter baumannii (ATCC 19606) and Methicillin-Resistant Staphylococcus Aureus (MRSA). Further, the clinical isolates of E. coli that are resistant and susceptible to antibiotics are utilized to test the efficacy of TA-AgNps. In E. coli, ESBLS are responsible for antibiotic resistance. Among, ESBLs CTXM-15 encoding gene is more prevalent in South India. Moreover, docking study with T. arjuna phytochemical constituents confirmed that the phytochemical constituents present in TA-AgNPs interacted well with CTXM-15 and highest interaction was observed with tannic acid. Hence the expression of gene encoding CTXM-15 was screened in clinical isolates. Interestingly, the expression of CTXM15 was not observed in samples treated with TA-AgNps. The results suggested that AgNPs of Terminalia arjuna bark extract can be used to control multidrug-resistant E. coli to prevent the antibiotic resistance. To the best of our knowledge, this is the first attempted study to show the effectiveness of Ta-AgNps against multidrug-resistant E. coli harbouring CTXM-15.