Abstract Organic electrochemical transistors (OECTs) have attracted considerable attention in the field of tissue‐interfaced bioelectronics. They uniquely bridge the ionic and electronic domains while offering mechanical compliance, biocompatibility, and high signal amplification. These characteristics make them especially advantageous for applications requiring stable, long‐term integration with soft, deformable, and dynamic biological tissues. This review provides a comprehensive summary of recent progress in the design, fabrication, and application of OECTs for biological integration. It begins by outlining the fundamental working mechanisms of OECTs and their advantages in transducing biological signals. Key strategies to enhance bio‐tissue interfacing are discussed, including molecular functionalization, interface orientation control, and mechanical matching. The review also covers developments in OECT‐based systems for skin‐mounted and implantable applications, with a focus on maintaining stability and responsiveness under dynamic physiological conditions. Particular attention is given to approaches that improve biocompatibility, reduce foreign body response, and enable minimally invasive operation in vivo. Finally, the article outlines key remaining challenges and suggests future directions to explore in this area.