In the present study, we evaluated the antibacterial and anti-quorum sensing qualities of phillyrin. The minimum inhibitory concentration (MIC) of phillyrin with regard to Pseudomonas aeruginosa is 0.5 mg/ml. The production of virulence factors—such as rhamnolipid (>78.69%), pyocyanin (>85.94%), and elastase (>89.95%)—that affect the pathogenicity of the P. aeruginosa strain PAO1 apparently declined in the presence of 0.25 mg/ml phillyrin. Biofilm formation decreased by 84.48%. In a Caenorhabditis elegans–Pseudomonas aeruginosa infection model, diseased worms lived longer (63.33%) in a phillyrin-containing medium than in a drug-free medium, and the drug did not directly kill the pathogen. Therefore, the present work suggests that phillyrin has potential as an antimicrobial agent for the control of infectious pathogens.