Background Since the introduction of active teaching methods, health science education has undergone considerable transformation. These methods help students become more motivated and develop communication, analytical and critical thinking skills, which influence students' learning practices. Aim The objective of this study is to evaluate effects of role-play simulation-based case studies on motivation and learning strategies among health sciences. Methods One hundred sixty-two students participated in this randomized trial. Students in the control group (n = 86) attended traditional interactive lectures, whereas students in the experimental group (n = 76) participated in role-play simulation-based case studies. The Motivated Strategies for Learning Questionnaire (MSLQ) was administered both before and after educational intervention for both groups. Results Compared to the control group, the scores of the experimental group are higher for Intrinsic goal orientation, Task value, Self-efficacy for learning and performance, Metacognitive self-regulation, Elaboration and critical thinking, Peer learning and help seeking (p< 0,001). In addition, we observed a positive association between role-play simulation-based case studies and Post-test sore of MLSQ for Task value, Self-efficacy for learning and performance, and Peer learning and help seeking (p < 0.05). Conclusions The study findings support the use of role-play simulation-based case studies in improving the motivation significantly and changing learning strategies for health care students. This active method can be recommended as a promising method for teaching health science.