Background: A designathon is a three-stage participatory activity informed by design thinking and rapid prototyping that includes preparation with end-users, an intensive period of collaborative teamwork, and evaluation of solutions by topic experts or community partners. A few previous systematic reviews have focused on the use of designathons in health. This study synthesised how designathons were organised and implementation-related factors to address health challenges. Methods: We searched Cochrane Library, Embase, PubMed, Scopus, and the ClinicalTrials.gov registry for peer-reviewed articles until November 29, 2022. The systemic review was registered in PROSPERO (CRD42023389685). Results: In total, 4,947 citations were identified, with 38 studies included in this review. Most studies were from high-income countries (26, 68%). The median number of participating teams was eight (IQR 5, 15), and the duration of the intensive collaboration phase ranged from three hours to seven days. The final products (i.e., ideas and prototypes) related to four themes: mobile applications, educational programs, medical devices, and other prototypes. Common evaluation criteria were feasibility, innovation or creativity, and impact. The most common facilitators were including diverse participants and having high-quality mentorship. . The most common barriers related to planning and implementing the designathon, and engaging diverse participants to participate. There were limited data on required resources and further implementation of solutions after designathons and no data on cost-effectiveness. Conclusion: Designathons are a promising tool for fostering innovative and person-centred solutions to address health challenges. Given its adaptability in terms of budget, mode of delivery, and involvement of diverse participants including end-users, designathons can be implemented in a wide range of contexts to address various health issues.