PURPOSE: In this study, the effect of a remotely supervised, home-based, family-centered individualized rehabilitation program of motor activities for individuals with Rett syndrome (RTT) was evaluated. MATERIALS AND METHODS: Thirteen participants with classic genetically confirmed RTT followed by a three-month program of motor activities at home. A total of 47 rehabilitative goals were set. Goals achievement, motor function, and parental satisfaction were evaluated. Each program was carried out by the participant's parents and remotely supervised via Skype calls, twice by a therapist experienced in RTT rehabilitation. RESULTS: Thirty-seven (78.7%) rehabilitative goals were achieved or overachieved. Ten participants (76.9%) significantly increased their gross motor functional level with a medium size effect (0.604). Parental reports of the involved families suggest, on average, a high level of usefulness of the program (4.4/5), adherence to the program (4.4/5), and general satisfaction (4.5/5). CONCLUSIONS: Our findings strongly support the implementation of such programs for this population. As these programs were remotely supervised, they can be implemented when the children are away from referenced facilities for long durations, such as during long holidays or a Covid-19 type lockdown.Implications for rehabilitationA remote supervised motor activity program carried out by the primary caregiver supports motor functioning in RTT.Therapists should consider family members' motivation to carry out the activities and integrate them into the family's daily routine.The program should be flexible to adapt to any sudden change in medical and environmental conditions, functional ability, and family members' motivational levels.