BACKGROUND: With the advent of smart sensing technology, mobile and wearable devices can provide continuous and objective monitoring and assessment of motor function outcomes. OBJECTIVE: We aimed to describe the existing scientific literature on wearable and mobile technologies that are being used or tested for assessing motor functions in mobility-impaired and healthy adults and to evaluate the degree to which these devices provide clinically valid measures of motor function in these populations. METHODS: A systematic literature review was conducted by searching Embase, MEDLINE, CENTRAL (January 1, 2015, to June 24, 2020), the United States and European Union clinical trial registries, and the United States Food and Drug Administration website using predefined study selection criteria. Study selection, data extraction, and quality assessment were performed by 2 independent reviewers. RESULTS: A total of 91 publications representing 87 unique studies were included. The most represented clinical conditions were Parkinson disease (n=51 studies), followed by stroke (n=5), Huntington disease (n=5), and multiple sclerosis (n=2). A total of 42 motion-detecting devices were identified, and the majority (n=27, 64%) were created for the purpose of health care-related data collection, although approximately 25% were personal electronic devices (eg, smartphones and watches) and 11% were entertainment consoles (eg, Microsoft Kinect or Xbox and Nintendo Wii). The primary motion outcomes were related to gait (n=30), gross motor movements (n=25), and fine motor movements (n=23). As a group, sensor-derived motion data showed a mean sensitivity of 0.83 (SD 7.27), a mean specificity of 0.84 (SD 15.40), a mean accuracy of 0.90 (SD 5.87) in discriminating between diseased individuals and healthy controls, and a mean Pearson r validity coefficient of 0.52 (SD 0.22) relative to clinical measures. We did not find significant differences in the degree of validity between in-laboratory and at-home sensor-based assessments nor between device class (ie, health care-related device, personal electronic devices, and entertainment consoles). CONCLUSIONS: Sensor-derived motion data can be leveraged to classify and quantify disease status for a variety of neurological conditions. However, most of the recent research on digital clinical measures is derived from proof-of-concept studies with considerable variation in methodological approaches, and much of the reviewed literature has focused on clinical validation, with less than one-quarter of the studies performing analytical validation. Overall, future research is crucially needed to further consolidate that sensor-derived motion data may lead to the development of robust and transformative digital measurements intended to predict, diagnose, and quantify neurological disease state and its longitudinal change.