<p>Mechanically conformal electrical and electrochemical biosensors serve as critical interfaces for reliable signal acquisition in dynamic biological environments. By matching the mechanical properties of soft tissues, these sensors overcome key limitations of conventional rigid platforms, including poor adhesion, signal fluctuation, and immune activation. Their ability to enable continuous and high-accuracy signal monitoring establishes them as foundational technologies in digital healthcare. This review outlines strategic approaches for developing mechanically conformal electrical and electrochemical biosensors, with a focus on material selection and fabrication, electrode design, and surface functionalization. It begins with an analysis of the mechanical properties of biological tissues and discusses the importance of modulus matching at bio-interfaces. Based on this framework, strategies to construct soft conductors with excellent electrical properties and mechanical adaptability are introduced, followed by design principles for compliant electrodes architectures and interfacial engineering. Finally, representative applications across cell/tissue/organ-on-a-chip, implantable, and wearable bioelectronics are highlighted, demonstrating their utility in electrophysiological monitoring, electrochemical sensing, and therapeutic intervention. Through a platform-specific perspective, this review provides insights into current challenges and future directions in field of mechanically conformal biosensors.</p>