Developing and communicating evidence-based explanations are regarded as essential skills in 21st-century learning. These skills are central to the process of scientific argumentation. Hence, teachers must adhere to a student-centered pedagogy that cultivates students' understanding and argumentation skills. This study investigated the effects of the Metacognitive Argument-Driven Inquiry (MADI) approach in promoting students' conceptual understanding of Antimicrobial Resistance and scientific argumentation skills. The study employed a mixed-method approach, which involved both quantitative and qualitative data. The participants were third-year Biological Science Education students (n=23) in a public university in Central Luzon, the Philippines. Quantitative data were obtained from the validated 30-item conceptual understanding test and six-point teacher-made written argumentation skills test, administered before and after students' four-week exposure to the MADI approach. Qualitative data from video-recorded sessions and focus group discussions were used to substantiate the quantitative findings. Descriptive and inferential statistics were utilized to determine if there were significant improvements at the end of the study. Results showed that students' conceptual understanding and argumentation skills significantly improved after exposure to the MADI approach with large effect sizes. Students' development of argumentation skills was evident during the implementation of the study, as seen in their increasing mean scores in each activity. Moreover, students signified the efficacy of the MADI approach in facilitating substantial improvements in their conceptual understanding and argumentation skills. Thus, it is suggested for Biology teachers to integrate the MADI approach in delivering their lessons and designing inquiry-based activities to support students' development of understanding and argumentation skills.