Low health literacy is a known contributing factor to poorer patient outcomes. Health information is often presented through materials written at high reading levels and thus may be an ineffective education tool for patients of diverse socioeconomic backgrounds, age ranges, and education levels. Graphic medicine (i.e., healthcare concepts presented through illustrations, such as comics or cartoons) may be a more equitable and efficacious format for many patients. The purpose of this review was to describe the efficacy and use of graphic medicine interventions regarding health outcomes, behavior changes, and engagement with health services. Nine databases were searched for studies that were randomized controlled trials in the English language, published before 4 December 2023. The searches identified 34 research articles that met the inclusion/exclusion criteria. This review revealed four key takeaways: (1) graphic medicine interventions are used globally; (2) graphic medicine interventions may be efficacious for a wide variety of health topics; (3) graphic medicine can be equitably delivered in many formats; and (4) graphic medicine can be applied broadly across the lifespan. The findings suggest that graphic medicine enhances patient engagement, empowers individuals with knowledge, and ultimately contributes to improved health outcomes across various populations; however, more effectiveness trials are needed. Additionally, an expanded definition of graphic medicine is presented.