The development of flexible electronic technology has led to significant advancements in wearable sensors. In the past decades, wearable chemosensors have received much attention from researchers worldwide due to their high portability, flexibility, lightweight, and adaptability. It allows real-time access to the user’s physiological status at the molecular level to analyze their health status. Therefore, it can be widely used in the field of precision medicine. This review introduces the sensing mechanisms of wearable chemosensors and recent progress in wearable sweat and interstitial fluid-based chemosensors. The complexities of wearable chemosensors are not to be underestimated, as there are considerable challenges in this field. This review aims to shed light on the difficulties associated with designing wearable sweat and interstitial fluid-based chemosensors and their potential development directions.