Research on gamification of learning has been very popular in the past years; especially, the learning effectiveness in applying games to the education of natural science in elementary and junior high schools has been proven. Aiming at the human blood circulation unit, which is rather difficult to comprehend, in the biology materials for junior high school students, Mobile Meaningful Blood Circulation Learning System, called MMBCLS game-based learning, is developed. The players could comprehend the functions of systemic circulation and pulmonary circulation through games. In the study, the instructional design is based on Meaningful Learning and follows the principles of digital game-based learning models to design the after-class multimedia materials, which allow learners enjoying learning with fun. The quasi-experimental design is utilized for the learning assessment, where the experimental group applies MMBCLS, while the control group uses general instruction for the teaching materials. The experimental results show significant difference of the experimental group in the learning effectiveness and better post-test results than the control group. The research outcomes could be the reference of material design for teachers and provide educators with the reference of mobile as meaningful media material design.