Triboelectric nanogenerators (TENGs) can not only collect mechanical energy around or inside the human body and convert it into electricity but also help monitor our body and the world by providing interpretable electrical signals during energy conversion, thus emerging as an innovative medical solution for both daily health monitoring and clinical treatment and bringing great convenience. This review tries to introduce the latest technological progress of TENGs for applications in biophysical sensors, where a TENG functions as a either a sensor or a power source, and in some cases, as both parts of a self-powered sensor system. From this perspective, this review begins from the fundamental working principles and then concisely illustrates the recent progress of TENGs given structural design, surface modification, and materials selection toward output enhancement and medical application flexibility. After this, the medical applications of TENGs in respiratory status, cardiovascular disease, and human rehabilitation are covered in detail, in the form of either textile or implantable parts for pacemakers, nerve stimulators, and nerve prostheses. In addition, the application of TENGs in driving third-party medical treatment systems is introduced. Finally, shortcomings and challenges in TENG-based biophysical sensors are highlighted, aiming to provide deeper insight into TENG-based medical solutions for the development of TENG-based self-powered electronics with higher performance for practical applications.