Millions of people with motor and cognitive disabilities face hardships in daily life due to the limited accessibility and inclusiveness of living spaces which limit their autonomy and independence. The DOMHO project deals with these fundamental issues by leveraging an innovative solution: a smart co-housing apartment. Besides, the project aims at exploiting the well know effects of co-housing on individuals’ health and well-being in combination with ambient assisted living technologies. The present study focused on the interaction of caregivers with the control application of an integrated smart system. Participants performed different tasks, fill out a questionnaire, and were interviewed. Performance and usability of the user interface, trust in technology, privacy, and attitudes towards home automation were explored. A series of guidelines for domotic technology control interfaces design was identified, and a high level of trust in these advanced tools was shown. Caregivers considered smart technologies as a work aid and a means for enhancing autonomy and life quality for users with disabilities.