Multiple sclerosis (MS) is a neurological disease of the central nervous system that is the leading cause of non-traumatic disability in young adults. Clinical laboratory tests and neuroimaging studies are the standard methods to diagnose and monitor MS. However, due to infrequent clinic visits, it is fundamental to identify remote and frequent approaches for monitoring MS, which enable timely diagnosis, early access to treatment, and slowing down disease progression. In this work, we investigate the most reliable, clinically useful, and available features derived from mobile and wearable devices as well as their ability to distinguish people with MS (PwMS) from healthy controls, recognize MS disability and fatigue levels. To this end, we formalize clinical knowledge and derive behavioral markers to characterize MS. We evaluate our approach on a dataset we collected from 55 PwMS and 24 healthy controls for a total of 489 days conducted in free-living conditions. The dataset contains wearable sensor data – e.g., heart rate – collected using an arm-worn device, smartphone data – e.g., phone locks – collected through a mobile application, patient health records – e.g., MS type – obtained from the hospital, and self-reports – e.g., fatigue level – collected using validated questionnaires administered via the mobile application. Our results demonstrate the feasibility of using features derived from mobile and wearable sensors to monitor MS. Our findings open up opportunities for continuous monitoring of MS in free-living conditions and can be used to evaluate and guide the effectiveness of treatments, manage the disease, and identify participants for clinical trials.