The antimicrobial activity and synergistic effect of four plant aqueous extracts their 1:1couple were evaluated against drug resistant strains of Escherichia coli and Pseudomonas aeruginosa. The MIC of the aqueous extracts of Green tea, Laura's nobilis, Rosmarinus officinalis and Ammi visnaga determined using resazurin microdilution method. Only green tea and Rosmarinus officinalis aqueous extracts and their combinations have antibacterial potency for both microorganisms with variable minimal inhibitory concentration (MIC). The results revealed a synergistic effect between both plants aqueous extracts with cefotaxime in both microorganisms. Also, a synergistic effect was found between nitrofurantoin and both plants extracts and between norfloxacin and rosemary extract for Pseudomonas aeruginosa. PCR confirmed the presence The pslA, exoS, qnrA, blaTEM genes on P. aeruginosa and stx2, iss, Mcr1, floR genes on E.coli . Using relative quantification RT-PCR revealed that Sub-MIC green tea extract highly reduced the relative genes expression of pslA, exoS, qnrA, blaTEM genes of P. aeruginosa , and stx2, iss, Mcr1, floR genes of E. coli compared to endogenous genes (16s rRNA). The results revealed the possibility of use of antimicrobial drugs and plant extracts in combination in treating infectious diseases caused by MDR microorganisms. Also, more research is required to investigate the interaction between the effects of plant extracts on the activity of antimicrobial agents and the effect of plants extracts on virulence and antimicrobial resistance genes expression of pathogenic bacteria.