Triboelectric nanogenerators (TENGs) are a promising power and sensing solution for biomedical applications attributed to the high electrical output and sensitivity with low-cost and widely available materials. Here, the recent developments in TENG-based biomedical applications with various structures and functionalities are discussed and summarized. Wearable TENGs perform well in motion and respiratory monitoring with excellent flexibility and low bio-risks. Implantable TENGs enable interactions with the cardio-cerebral vascular system and nervous system to monitor and treat different diseases with good biodegradability. Furthermore, explorations of TENGs in in vitro systems, including drug delivery, cellular proliferation and differentiation, are reviewed. Perspectives on the biomedical applications of TENGs are proposed based on investigation in this area in the past two decades. With continuous efforts in miniaturization and optimization of robustness, the TENG-based self-powered biomedical systems will definitely play an important role in the healthcare market in the future. K E Y W O R D S biomedical systems, in vitro systems, in vivo applications, triboelectric nanogenerators 1 | INTRODUCTION Disease prevention, diagnosis, and therapy are attractive research topics since they are essential to human health. Accordingly, precise signal monitoring of health-related physiological parameters, which can reflect the health conditions of patients in real time, is of paramount importance. 1-4 Current instruments for clinical diagnosis, such as electrocardiograph (ECG) monitor, electroencephalograph (EEG), gastroscope, and enteroscope, are usually bulky, and it is hard to upgrade them into wearable devices to realize in vivo real-time monitoring. 5 Additionally, clinical instruments for therapeutic purposes such as using the pulse generator to stimulate brain are usually expensive, which hinders their wider applications and more frequent use on patients. Low-cost portable, wearable, and implantable devices are urgently required to meet the demands of in vivo health monitoring and disease treatment. 6,7 Rapid development in flexible materials and technologies has given rise to the emergence of wearable Xin Xia and Qing Liu contribute equally to this work.