Flexible and stretchable biosensors have the advantage of enhanced signal validity and patient comfort during physiological signal sensing and biomolecular analysis, crucial for disease diagnosis, treatment and health management. Their lightness, softness and excellent mechanical properties enable effective skin-device interface coupling and skin safety profiles, realizing multi-functional, intelligent real-time sensing. In this review, the basic sensing principles of biosensor systems and their applications are discussed. Moreover, the potential applications and prospective progress of these biosensors are further prospected. Flexible, wearable biosensors have the potential to realize continuous and long-term health monitoring in clinical and daily health care.