The rapid proliferation of mobile devices and advancements in wireless technologies have given rise to a new era of healthcare delivery through mobile health (mHealth) applications. Design Science Research (DSR) is a widely used research paradigm that aims to create and evaluate innovative artifacts to solve real-world problems. This paper presents a comprehensive framework for employing DSR in mHealth application projects to address healthcare challenges and improve patient outcomes. We discussed various DSR principles and methodologies, highlighting their applicability and importance in developing and evaluating mHealth applications. Furthermore, we present several case studies to exemplify the successful implementation of DSR in mHealth projects and provide practical recommendations for researchers and practitioners.