<p>Advancements in bioelectronics are revolutionizing traditional healthcare by shifting the focus from in-hospital disease diagnosis and treatment to at-home continuous preventive care. This transformation integrates real-time health monitoring and point-of-care interventional therapies and enables artificial intelligence-based health management strategies. However, the mechanical mismatch between rigid bioelectronic devices and soft biological tissues presents important challenges, particularly in long-term applications, including poor adhesion, tissue degeneration, high noise level, signal interference and device instability. To address these challenges, soft bioelectronics — leveraging high-performance, tissue-mimicking and mechanically soft materials — has emerged as a disruptive solution. This Review highlights advancements in materials design and system-level integration strategies for soft bioelectronics, driving the development of next-generation digital healthcare technologies. We categorize materials design approaches, introduce fabrication techniques for soft bioelectronics and explore integration methods. Furthermore, we showcase applications of wearable and implantable soft bioelectronics, demonstrating their potential for continuous health monitoring and therapeutic interventions, ultimately enabling closed-loop health management.</p>