{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:22:13Z","timestamp":1793726533103,"version":"4.6.1"},"reference-count":336,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF)","award":["RS-2023-00241461"],"award-info":[{"award-number":["RS-2023-00241461"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Foundation of Korea (NRF)","award":["RS-2021-NR060118"],"award-info":[{"award-number":["RS-2021-NR060118"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Education","award":["RS-2023-00241461"],"award-info":[{"award-number":["RS-2023-00241461"]}]},{"name":"Ministry of Education","award":["RS-2021-NR060118"],"award-info":[{"award-number":["RS-2021-NR060118"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Biofilms are complex microbial communities encased within a self-produced extracellular matrix, which plays a critical role in chronic infections and antimicrobial resistance. These enhance pathogen survival and virulence by protecting against host immune defenses and conventional antimicrobial treatments, posing substantial challenges in clinical contexts such as device-associated infections and chronic wounds. Secondary metabolites derived from medicinal plants, such as alkaloids, tannins, flavonoids, phenolic acids, and essential oils, have gained attention as promising agents against biofilm formation, microbial virulence, and antibiotic resistance. These natural compounds not only limit microbial growth and biofilm development but also disrupt communication between bacteria, known as quorum sensing, which reduces their ability to cause disease. Through progress in nanotechnology, various nanocarriers such as lipid-based systems, polymeric nanoparticles, and metal nanoparticles have been developed to improve the solubility, stability, and cellular uptake of phytochemicals. In addition, the synergistic use of plant-based metabolites with conventional antibiotics or antifungal drugs has shown promise in tackling drug-resistant microorganisms and revitalizing existing drugs. This review comprehensively discusses the efficacy of pure secondary metabolites from medicinal plants, both as individuals and in nanoformulated forms or in combination with antimicrobial agents, as alternative strategies to control biofilm-forming pathogens. The molecular mechanisms underlying their antibiofilm and antivirulence activities are discussed in detail. Lastly, the current pitfalls, limitations, and emerging directions in translating these natural compounds into clinical applications are critically evaluated.<\/jats:p>","DOI":"10.3390\/antibiotics14060555","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T09:47:34Z","timestamp":1748512054000},"page":"555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Multiple Strategies for the Application of Medicinal Plant-Derived Bioactive Compounds in Controlling Microbial Biofilm and Virulence Properties"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0355-7732","authenticated-orcid":false,"given":"Mulugeta","family":"Mulat","sequence":"first","affiliation":[{"name":"Department of Biotechnology, School of Bioscience and Technology, College of Natural Sciences, Wollo University, Dessie 1145, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2641-9290","authenticated-orcid":false,"given":"Riza Jane S.","family":"Banicod","sequence":"additional","affiliation":[{"name":"Fisheries Postharvest Research and Development Division, National Fisheries Research and Development Institute, Quezon City 1128, Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9314-9124","authenticated-orcid":false,"given":"Nazia","family":"Tabassum","sequence":"additional","affiliation":[{"name":"Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Research Center for Marine Integrated Bionics Technology, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aqib","family":"Javaid","sequence":"additional","affiliation":[{"name":"Interdisciplinary Program of Marine and Fisheries Sciences and Convergent Technology, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abirami","family":"Karthikeyan","sequence":"additional","affiliation":[{"name":"Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9121-851X","authenticated-orcid":false,"given":"Geum-Jae","family":"Jeong","sequence":"additional","affiliation":[{"name":"Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Research Center for Marine Integrated Bionics Technology, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Department of Food Science and Technology, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2465-8013","authenticated-orcid":false,"given":"Young-Mog","family":"Kim","sequence":"additional","affiliation":[{"name":"Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Research Center for Marine Integrated Bionics Technology, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Department of Food Science and Technology, Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1615-750X","authenticated-orcid":false,"given":"Won-Kyo","family":"Jung","sequence":"additional","affiliation":[{"name":"Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Research Center for Marine Integrated Bionics Technology, Pukyong National University, Busan 48513, Republic of Korea"},{"name":"Major of Biomedical Engineering, Division of Smart Healthcare, College of Information Technology and Convergence and New-Senior Healthcare Innovation Center (BK21 Plus), Pukyong National University, Busan 48513, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4902-3188","authenticated-orcid":false,"given":"Fazlurrahman","family":"Khan","sequence":"additional","affiliation":[{"name":"Marine Integrated 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