As an evolutionary success in life science, wearable biosensor systems, which can monitor human health information and quantify vital signs in real time, have been actively studied. Research in wearable biosensor systems is mainly focused on the design of sensors with various flexible materials. Among them, 2D materials with excellent mechanical, optical, and electrical properties provide the expected characteristics to address the challenges of developing microminiaturized wearable biosensor systems. This review summarizes the recent research progresses in 2D-materials-based wearable biosensors including e-skin, contact lens sensors, and others. Then, we highlight the challenges of flexible power supply technologies for smart systems. The latest advances in biosensor systems involving wearable wristbands, diabetic patches, and smart contact lenses are also discussed. This review will enable a better understanding of the design principle of 2D biosensors, offering insights into innovative technologies for future biosensor systems toward their practical applications.