Aim: Inhibition of some quorum sensing (QS) regulated virulence factors via using non-antibiotic helping drugs to overcome antibiotic resistance problem. Introduction: P. aeruginosa is one of the major causes of fatal health care-associated infection. P. aeruginosa's virulence factors are highly controlled by QS systems which lead to antibiotics resistance. Targeting QS may be a promising therapeutic hope for P. aeruginosa infections. Methods: Molecular Docking was performed by Shroedinger 2016 using the required constraints in the binding sites of the Las & Rhl receptor proteins of P. aeruginosa to estimate the expected activity of (quercetin and meloxicam) and compare them with great docking scores compounds like rosmarinic acid. PAO1 was used as reference strain with other P. aeruginosa strains (clinical samples). An antibiotic sensitivity test was performed to evaluate antibiotic resistance. The minimum inhibitory concentration (MIC) of tested drugs were also measured against the resistant strains. Virulence factors thanked for QS (protease, pyocyanine, rhamnolipids) and biofilm formation of selected strains were assessed before and after treatment with quercetin & meloxicam. Results and conclusion: In silico studies indicated that quercetin and meloxicam could act as inhibitors for the auto-inducer molecules as they have a high affinity for the regulatory proteins of the QS system lasR and rhlR. The experimental study of quercetin and meloxicam against P. aeruginosa showed that at sub-MIC, both drugs reduced biofilm formation and some tested virulence factors. Treatment of P. aeruginosa infection using QS inhibitors is expected and this approach may overcome the antibiotic resistance problem.