BACKGROUND: Earable devices are novel, wearable Internet of Things devices that are user-friendly and have potential applications in mobile health care. The position of the ear is advantageous for assessing vital status and detecting diseases through reliable and comfortable sensing devices. OBJECTIVE: Our study aimed to review the utility of health-related indicators derived from earable devices and propose an improved definition of disease prevention. We also proposed future directions for research on the health care applications of earable devices. METHODS: A systematic review was conducted of the PubMed, Embase, and Web of Science databases. Keywords were used to identify studies on earable devices published between 2015 and 2020. The earable devices were described in terms of target health outcomes, biomarkers, sensor types and positions, and their utility for disease prevention. RESULTS: A total of 51 articles met the inclusion criteria and were reviewed, and the frequency of 5 health-related characteristics of earable devices was described. The most frequent target health outcomes were diet-related outcomes (9/51, 18%), brain status (7/51, 14%), and cardiovascular disease (CVD) and central nervous system disease (5/51, 10% each). The most frequent biomarkers were electroencephalography (11/51, 22%), body movements (6/51, 12%), and body temperature (5/51, 10%). As for sensor types and sensor positions, electrical sensors (19/51, 37%) and the ear canal (26/51, 51%) were the most common, respectively. Moreover, the most frequent prevention stages were secondary prevention (35/51, 69%), primary prevention (12/51, 24%), and tertiary prevention (4/51, 8%). Combinations of ≥2 target health outcomes were the most frequent in secondary prevention (8/35, 23%) followed by brain status and CVD (5/35, 14% each) and by central nervous system disease and head injury (4/35, 11% each). CONCLUSIONS: Earable devices can provide biomarkers for various health outcomes. Brain status, healthy diet status, and CVDs were the most frequently targeted outcomes among the studies. Earable devices were mostly used for secondary prevention via monitoring of health or disease status. The potential utility of earable devices for primary and tertiary prevention needs to be investigated further. Earable devices connected to smartphones or tablets through cloud servers will guarantee user access to personal health information and facilitate comfortable wearing.