Pseudomonas aeruginosa is a significant contributor to food spoilage and foodborne diseases. The primary strategy for preventing and controlling contamination by P. aeruginosa involves the application of antibacterial agents. However, the overuse or abuse of antimicrobial agents has accelerated the development of drug resistance. The control of spoilage and antimicrobial resistance in P. aeruginosa has emerged as a major food safety challenge. Numerous studies have established that the pathogenicity and drug resistance of P. aeruginosa are regulated by quorum sensing (QS). Therefore, inhibiting the QS system of P. aeruginosa is a promising approach to mitigate the pathogenicity and resistance of this pathogen. This review explores various QS systems of P. aeruginosa and their roles in bacterial pathogenesis and drug resistance. Additionally, it discusses the potential of small chemical molecules and quorum-quenching enzymes in attenuating the pathogenesis of P. aeruginosa, as well as the possibility of using QS inhibitors (QSIs) and antibiotics in future therapeutic approaches for P. aeruginosa-associated infections.