Pseudomonas aeruginosa is a leading cause of life-threatening nosocomial infections. P. aeruginosa virulence factors are largely directed by quorum sensing (QS) systems which leads to extreme resistance to multiple antibiotics. QS may be considered an important therapeutic target to combat P. aeruginosa infections. Methods: Docking analysis was preformed through Shroedinger 2016 using the required constraints in the binding sites of the las & Rhl receptor proteins of P. aeruginosa to assess the expected activity of (quercetin and meloxicam) and compare them with other compounds showed high docking scores like rosmarinic acid. laboratory strain P. aeruginosa PAO1 was used as a reference strain, and other P. aeruginosa strains were clinicaly isolated. Antibiotic sensitivity test was performed to select strains resistant to multiple antibiotics. The minimum inhibitory concentration (MIC) of tested drugs were also measured against the selected strains. QS controlled virulence factors (elastine, protease, pyocyanine, hemolysine, rhamnolipids, motility) and biofilm formation of selected strains were assessed before and after treatment with quercetin & meloxicam. Results and conclusion: In silico studies revealed that quercetin and meloxicam could serve as a competitive inhibitor for the auto-inducer molecules as they exhibited a strong affinity for the regulatory proteins of the QS circuits i.e. LasI and RhlR. The experimental assessment of quercetin and meloxicam against P. aeruginosa showed that: At sub-MIC, both drugs suppressed the production of QS-controlled biofilm formation and other tested virulence factors. Promising improvement in P.aeruginosa infection treatment using quourm sensing inhibitors and this approach may reduce antibiotic overuse and selection pressure.