In the EU funded MARIO project, specific technological tools are adopted for the patient with dementia (PWD). At this stage of the project, the experimentation phase is under way, and the first two trials were completed as shown below: the first trial was performed in November 2016, and second trial was performed in April 2017. The current implemented and assessed applications (apps) are My Music app, My News app, My Games app, My Calendar app, My Family and Friends app, and Comprehensive Geriatric Assessment (CGA) app. The aim of the present study was to provide a preliminary analysis of the acceptability and efficacy of MARIO companion robot on clinical, cognitive, neuropsychiatric, affective and social aspects, resilience capacity, quality of life in PWD, and burden level of the caregivers. Thirteen patients [5 patients (M = 3; F = 2) in first trial, and 8 patients (M = 6; F = 2) in second trial] were screened for eligibility and all were included. At admission and at discharge, the following tests were administered: Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Clock Drawing Test (CDT), Frontal Assessment Battery (FAB), Hachinski Ischemic Scale (HIS), Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS), Hamilton Rating Scale for Depression (HDRS-21), Multidimensional Scale of Perceived Social Support (MSPSS), Social Dysfunction Rating Scale (SDRS), Brief Resilience Scale (BRS), Quality of Life in Alzheimer’s Disease (QOL-AD), Caregiver Burden Inventory (CBI), Tinetti Balance Assessment (TBA), and Comprehensive Geriatric Assessment (CGA) was carried out. A questionnaire based on the Al-mere Acceptance model was used to evaluate the acceptance of the MARIO robot. During the first trial, My Music, My Games and My News apps were used. At discharge, no significant improvement was shown through the above questionnaires. During the second trial, My Music, My Games, My News, My Calendar, My Family and Friends, and CGA apps were used. At discharge, significant improvements were observed in the following parameters: NPI (p = 0.027), GDS-15 (p = 0.042), and BRS (p = 0.041), CBI (p = 0.046). Instead, the number of medications is increased at discharge (p = 0.038). The mean of hospitalization days is 5.6 ± 3.9 (range = 3–13 days). The Almere Model Questionnaire suggested, a higher acceptance level was shown in first and second trial.