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Covalent organic frameworks (COFs) exhibit significant potential in photocatalytic antibacterial applications, but face challenges such as insufficient biosafety and difficulties in application translation. In this work, we first report two metformin\u2010based photoactive cationic MCOFs engineered for synergistic functionality and safety. They exhibit broad\u2010spectrum light absorption, efficient charge separation, and generate multiple ROS via Type I\/II photodynamic, achieving &gt;99 % inactivation of bacteria\/viruses. Excellent biocompatibility with LD\n                    <jats:sub>50<\/jats:sub>\n                    &gt;5000\u00a0mg\/kg is confirmed. Mechanistic studies based on molecular dynamics (MD) simulation and transcriptome results revealed a triple synergistic antibacterial pathway involving membrane targeting, ROS attack, and metabolic interference. Furthermore, we fabricated a COF\/thermoplastic polyurethane (TPU) composite functional membrane, which exhibits &gt;99 % antibacterial and antiviral efficiency, along with a notable 98.3 % inhibition rate against methicillin\u2010resistant Staphylococcus aureus (MRSA). This study not only provides a new design strategy for MCOFs with synergistically enhanced functionality and biosafety, but also offers a promising material platform for biomedical applications such as anti\u2010infection protection, wound healing, and the treatment of drug\u2010resistant bacterial infections.\n                  <\/jats:p>","DOI":"10.1002\/advs.202522437","type":"journal-article","created":{"date-parts":[[2025,12,27]],"date-time":"2025-12-27T10:12:23Z","timestamp":1766830343000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Metformin\u2010Based Covalent Organic Frameworks With Excellent Biosafety and High Efficiency against Pathogenic Microorganisms"],"prefix":"10.1002","volume":"13","author":[{"given":"Jia\u2010Yi","family":"Liu","sequence":"first","affiliation":[{"name":"Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target &amp; Clinical Pharmacology the NMPA and State Key Laboratory of Respiratory Disease School of Pharmaceutical Sciences Guangzhou Medical University  Guangzhou P. 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