Background Iatrogenic hypoglycemia is a common occurrence among hospitalized patients and is associated with poor clinical outcomes and increased mortality. Clinical decision support systems can be used to reduce the incidence of this potentially avoidable adverse event. Objective This study aims to determine the desired features and functionality of a real-time informatics alert to prevent iatrogenic hypoglycemia in a hospital setting. Methods Using the Agency for Healthcare Research and Quality Five Rights of Effective Clinical Decision Support Framework, we conducted a mixed methods study using an electronic survey and focus group sessions of hospital-based providers. The goal was to elicit stakeholder input to inform the future development of a real-time informatics alert to target iatrogenic hypoglycemia. In addition to perceptions about the importance of the problem and existing barriers, we sought input regarding the content, format, channel, timing, and recipient for the alert (ie, the Five Rights). Thematic analysis of focus group sessions was conducted using deductive and inductive approaches. Results A 21-item electronic survey was completed by 102 inpatient-based providers, followed by 2 focus group sessions (6 providers per session). Respondents universally agreed or strongly agreed that inpatient iatrogenic hypoglycemia is an important problem that can be addressed with an informatics alert. Stakeholders expressed a preference for an alert that is nonintrusive, accurate, communicated in near real time to the ordering provider, and provides actionable treatment recommendations. Several electronic medical record tools, including alert indicators in the patient header, glucose management report, and laboratory results section, were deemed acceptable formats for consideration. Concerns regarding alert fatigue were prevalent among both survey respondents and focus group participants. Conclusions The design preferences identified in this study will provide the framework needed for an informatics team to develop a prototype alert for pilot testing and evaluation. This alert will help meet the needs of hospital-based clinicians caring for patients with diabetes who are at a high risk of treatment-related hypoglycemia.