Bio-adhesives used clinically, commonly have the ability to fill surgical voids and support wound healing, but which are devoid of antibacterial activity, and thus, could not meet the particular needs of the infected wound site. Herein, a series of natural polyphenolic antibacterial bio-adhesives were prepared via simple mixing and heating of polyphenols and acid anhydrides without any solvent or catalyst. Upon the acid anhydride ring opening and acylation reactions, various natural polyphenolic bio-adhesives could adhere to various substrates (i.e., tissue, wood, glass, rubber, paper, plastic, and metal) based on multi-interactions. Moreover, these bio-adhesives showed excellent antibacterial and anti-infection activity, rapid hemostatic performance and appropriate biodegradability, which could be widely used in promoting bacterial infection wound healing and hot burn infection wound repair. This work could provide a new strategy for strong adhesives using naturally occurring molecules, and provide a method for the preparation of novel multifunctional wound dressings for infected wound healing.