Background: Multiple Sclerosis (MS) is a chronic disease with a high prevalence of neuropsychiatric symptoms. Mindfulness is a practice that encourages individuals to cultivate a present-focused, acceptance-based approach for managing neuropsychiatric symptoms. Its positive effect on MS has been demonstrated, but learning such technique is expensive and time-consuming. In this study, we investigated the feasibility and efficacy of an 8-week, at-home, technology-supported mindfulness program in a cohort of MS patients. Methods: The study included two visits, one at baseline and another after the mindfulness program. We measured adherence to the proposed mindfulness treatment and its effect on different neuropsychological scales and in terms of quantitative EEG parameters. All participants received a smart biofeedback device to be used during the therapeutic program consisting of daily meditative exercises. Results: Twenty-nine patients were recruited for the present study. Among them, 27 (93%) completed the entire program and 17 (63%) completed more than 80% of the scheduled sessions. We observed a statistically significant reduction of the Ruminative Response Scale score and a significant increase in the Digit Span Backward. Regarding neurophysiological data, we found a significant reduction of the whole-scalp beta and parieto-occipital theta power post intervention. Conclusion: Our results show that an at-home, technology-supported mindfulness program is feasible for people with MS. The efficacy in terms of reappraisals of stress, cognitive and emotional coping responses is also supported by our neurophysiological data. Further studies are warranted to better explore the role of such approaches in managing the psychological impact of MS diagnosis.