Bioadhesive technologies are important in a wide range of applications, spanning from wound management to wearable technologies. Forming and controlling tough adhesion on biological tissues has been a long-lasting challenge, necessitating transdisciplinary approaches. In my talk, I will share our recent progress in the design, mechanics, and applications of tough bioadhesives. I will first discuss the limitations of clinically used surgical glues and blood clots in terms of adhesion properties. I will then present the mechanical principles for making tough bioadhesives that exhibit superior adhesion performance on diverse tissues. Furthermore, I will discuss our transdisciplinary approaches and underlying mechanisms for controlling tough bioadhesion through ultrasound and interfacial entanglements. Lastly, I will showcase the applications of tough bioadhesives in wound management, tissue repair, and hemorrhage control. This talk will highlight the synergy of materials and mechanics in the development of new biomaterials poised to address clinical challenges.