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Pseudomonas aeruginosa is gram-negative bacteria with high adaptability by forming biofilms and quorum-sensing mechanisms to avoid immune responses and antimicrobial agents which tend to develop into Multidrug Resistance (MDR) related to Healthcare-Associated Infection (HAI) with a prevalence of 3,8% in Indonesia and a mortality of up to 69%. Polyphenol compounds found in pomelo peels ( Citrus maxima ) have been shown to have antibiofilm and antiquorum-sensing effects but are less investigated. Therefore, this study aimed to investigate those effects on MDR P. aeruginosa . In vitro study design is performed to evaluate the inhibition effect of ethanolic extract on bacterial growth (Kirby-Bauer test), biofilm formation (biofilm assay), and quorum-sensing activity (pyocyanin and pyoverdine assay) on clinical isolates of MDR and ATCC strain as comparator. Furthermore, we employed computational methods using docking protein analysis. Biofilm formation was significantly inhibited by 71.1% ± 4.4% in MDR (pLasR and LasI ) by active compounds of Citrus maxima . Molecular docking was used to further strengthen this hypothesis, showing no significant differences in bonding energy of polyphenol compounds found in pomelo peel with LasR and LasI compared to the native ligand and inhibitors. Pomelo peel extract can be considered as a potential therapy for MDR P. aeruginosa infection mediated based on its antibiofilm and antiquorum-sensing effects., Competing Interests: Conflict of interest The authors declare there is no conflict of interest in this study., (© the Author(s).)