Background: Although the Positive emotion, Engagement, Relationship, Meaning in life and Accomplishment (PERMA) model and students' well-being have been growing concerns in English language teaching (ELT) in recent years, experimental research in ELT examining the effects and mutual relationship of these two concepts on student learning remains scarce. As a part of a larger project, this study, therefore, explored the impact of PERMA-based speaking lessons in English for Medical Purposes (EMP) courses on students' well-being. The results were expected to contribute to enriching the existing literature and shed light on the effects of the PERMA model in ELT. Methods: The study employed a counterbalanced experimental design. Data were collected from two participant groups: 38 General Medicine students (Group 1) and 41 Odonto-Stomatology students (Group 2), who received the intervention program at two different intervals. A questionnaire administered before and after each intervention phase served as the primary data collection tool. The data were analyzed using the Repeated Measures Analysis of Variance (ANOVA) test by SPSS, version 22. Results: The findings indicate that the PERMA-based speaking lessons enhanced students' well-being while reducing their negative feelings during English speaking activities, though more analysis is needed to be done to understand the effects of the PERMA-based lessons on the changes in students' negative feelings. Conclusion: The PERMA-based lessons have a positive influence on students' learning in English speaking classes. Therefore, the multiplication of this model application in ELT can help boost students' learning well-being and thus be beneficial for students' development.