Access to mobile learning (mLearning) opportunities has become widespread and continues to proliferate as a means of educational continuity during the COVID-19 pandemic. Due to such proliferation, guidance is needed to inform the design of mobile learning content from both learning and accessibility perspectives. Though evidence-based recommendations for mobile learning message design do not currently exist, prior research in multimedia learning and instructional design-related areas may be used to support the planning and production of such educational programming. Design efforts for mLearning would also benefit from the incorporation of strategies to enhance the accessibility of mLearning for learners with differing needs. Taking evidence-based practices from instructional design and universal design for learning could inform the future development of mLearning toward more effective learning experiences for all learners. Employing a design and development methodology, this study focused on the creation of evidence-based guidelines for mLearning content design, informed by prior research on instructional message design combined with recognized universal design principles for media-based learning. The study resulted in a set of considerations to guide the message design of accessible and effective mLearning experiences. The resulting guidelines underwent validation by expert reviewers representing the areas of instructional design, message design, universal design, and mLearning. Their feedback informed the final version of the guidelines produced as the outcome of this study, research-based considerations which can be practically applied by those responsible for the creation of mLearning instruction.