Acinetobacter baumannii is an inescapable pathogen capable of causing both community and health care–associated infections (HAIs). It has recently emerged as a major cause of HAI, because of its tendency of antimicrobial resistance mechanisms that has the proclivity for pan-drug resistance and cause large outbreaks in many institutes. Aims and Objective: The study aimed to investigate the antimicrobial susceptibility test and the biofilm production of the A. baumannii isolates. The study further aims to perform the real time PCR test for confirmatory identification and detection of drug resistance genes of A. baumannii. We also aimed to evaluate the selected natural products against antimicrobial resistance A. baumannii toward novel therapeutic agent. Methods: Around 100 positive of A. baumannii were taken from various clinical samples. Acinetobacter baumannii showed least sensitivity (14%-92%) to almost all the drugs and was 100% sensitive only to colistin and tigecycline. Various drug resistant genes like blaOXA 23, blaOXA 24, ,bla VIM-1 and blaSIM-1 genes were detected using real time PCR. The antimicrobial activity of Cleistanthus bracteosus Jabl on the A. baumannii isolates was found to be sensitive when compared to carbapenem drugs. Conclusion: The results suggest that other therapeutics options are needed apart from the antimicrobial agents. The study will further provide an important aid for discovering new antibiotics and determining efficient combination therapy, which are essential strategies for combating multidrug-resistant A. baumannii infections.