This study evaluates mobility in patients with multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and Parkinson’s disease (PD) by integrating clinical assessments, instrumented gait analysis (IGA) in the hospital, and 1 week of physical activity monitoring (PAM) at home, using wearable sensors. Clinical scores provide a broad measure of disease severity but lack precision in quantifying gait impairments. IGA offers objective gait metrics under standardized conditions, identifying deficits in stride dynamics and postural control. However, these controlled assessments do not reflect real-world mobility. PAM addresses this gap by continuously tracking movement patterns and physical activity during daily-life, offering insights into how patients walk beyond clinical settings. The combination of IGA and PAM provides a more comprehensive understanding of mobility limitations, particularly in MSA and PSP, where gait and balance impairments differ from PD. This dual approach enhances patient assessment, supports personalized disease management, and improves clinical decision-making. Trial registration: ClinicalTrials.gov, NCT04608604, date of registration: 19/10/2020, first patient enrollment: 01/02/2021.