Justification: Providing care to patients with several conditions and simultaneously taking several medications at home is inexorably growing in developed countries. This trend increases the chances of home caregivers experiencing diverse errors related with medication or care. Objective: To determine the effectiveness of four different educational solutions compared to the natural intervention (absence of intervention) to provide a safer care at home by caregivers. Method: Prospective, parallel, and mixed research study with two phases. Candidates: Home-based caregivers caring a person with multiple comorbid conditions or polymedication who falls into one of the three profiles of patients defined for the study (oncology, cardiovascular, or pluripathological patients). First phase: Experts first answered an online survey, and then joined together to discuss the design and plan the content of educational solutions directed to caregivers including the identification of medication and home care errors, their causes, consequences, and risk factors. Second phase: The true experiment was performed using an inter- and intrasubject single-factor experimental design (five groups: four experimental groups against the natural intervention (control), with pre- and post-intervention and follow-up measures) with a simple random assignment, to determine the most effective educational solution (n = 350 participants). The participants will be trained on the educational solutions through 360 V, VR, web-based information, or psychoeducation. A group of professionals called the “Gold Standard” will be used to set a performance threshold for the caring or medication activities. The study will be carried out in primary care centers, hospitals, and caregivers’ associations in the Valencian Community, Andalusia, Madrid, and Murcia. Expected results: We expect to identify critical elements of risk management at home for caregivers and to find the most effective and optimal educational solution to reduce errors at home, increasing caregivers’ motivation and self-efficacy whilst the impact of gender bias in this activity is reduced. Trial Registration: Clinical Trial NCT05885334.