The essence of Genetics lies in the understanding of the concepts of Central Dogma of Molecular Biology. Although these ideas are fundamental to the field, they are notoriously difficult to understand and visualize. While simulation-based instructional materials are found to improve the teaching-learning process in science education, little has been done to assess their effectiveness in teaching and learning the concepts of Central Dogma of Molecular Biology. Hence, this study aimed to examine the effectiveness of simulation-based instructional materials towards the learning performance of Grade 12 learners on the concepts of Central Dogma of Molecular Biology. This study utilized a mixed-method approach. Results of the pretest and posttest showed that the learners demonstrated from approaching proficiency to advanced mastery level on the concepts of Central Dogma of Molecular Biology. Furthermore, it was revealed that the pretest and posttest mean scores of the learners on the concepts differed significantly (p<0.05). The result of the semi-structured interview revealed that the learners were engaged in experiential learning with the use of simulation-based instructional materials. An action plan was designed based on the study to utilize the simulation-based instructional materials in the teaching-learning process.