Skin-electronic interfaces have broad applications in fields such as diagnostics, therapy, health monitoring, and smart wearables. However, they face various challenges in practical use. For instance, in wet environments, the cohesion of the material may be compromised, and under dynamic conditions, maintaining conformal adhesion becomes difficult, leading to reduced sensitivity and fidelity of electrical signal transmission. The key scientific issue lies in forming a stable and tight mechanical-electronic coupling at the tissue-electronic interface. Here, inspired by octopus sucker structures and snail mucus, we propose a strategy for hydrogel skin-electronic interfaces based on multi-coupled bioinspired adhesion and introduce an ultrasound (US)-mediated interfacial toughness enhancement mechanism. Ultimately, using digital light processing micro-nano additive manufacturing technology (DLP 3D), we have developed a multifunctional, diagnostic-therapeutic integrated patch (PAMS). This patch exhibits moderate water swelling properties, a maximum deformation of up to 460%, high sensitivity (GF = 4.73), and tough and controllable bioadhesion (shear strength increased by 109.29%). Apart from outstanding mechanical and electronic properties, the patch also demonstrates good biocompatibility, anti-bacterial properties, photothermal properties, and resistance to freezing at −20 °C. Experimental results show that this skin-electronic interface can sensitively monitor temperature, motion, and electrocardiogram signals. Utilizing a rat frostbite model, we have demonstrated that this skin-electronic interface can effectively accelerate the wound healing process as a wound patch. This research offers a promising strategy for improving the performance of bioelectronic devices, sensor-based educational reforms and personalized diagnostics and therapeutics in the future. Statement of significanceEstablishing stable and tight mechanical-electronic coupling at the tissue-electronic interface is essential for the diverse applications of bioelectronic devices. This study aims to develop a multifunctional, diagnostic-therapeutic integrated hydrogel skin-electronic interface patch with enhanced interfacial toughness. The patch is based on a multi-coupled bioinspired adhesive-enhanced mechanism, allowing for personalized 3D printing customization. It can be used as a high-performance diagnostic-therapeutic sensor and effectively promote frostbite wound healing. We anticipate that this research will provide new insights for constructing the next generation of multifunctional integrated high-performance bioelectronic interfaces.