Herein, we report the synthesis and screening of linezolid-like Schiff bases as inhibitors of biofilm formation. The result of biofilm inhibition of Pseudomonas aeruginosa suggested that compounds 5h (IC50 value=12.97±0.33μM) and 5i (IC50 value=15.63±0.20μM) had more inhibitory activity when compared with standard linezolid (IC50=15.93±0.18μM) without affecting the growth of cells (and thus behave as anti-quorum sensing agents). The compounds 5h (MIC range=2.5-10μg/mL) and 5i (MIC range=3.5-10μg/mL) with 2-chloroquinolinyl and 2-chloro-8-methylquinolinyl motif, respectively, showed antibacterial activity in comparable range of linezolid (MIC range=2-3μg/mL) and were more potent when compared with ciprofloxacin (MIC range=25-50μg/mL). Thus, the active derivatives were not only potent inhibitors of P. aeruginosa biofilm growth but also efficient antibacterial agents. The docking study of most active compounds 5h and 5i against PqsD enzyme of P. aeruginosa exhibited good binding properties. In silico ADME properties of synthesized compounds were also analyzed and showed potential to develop as good oral drug candidates.