The aim of this study is to investigate the effects of the flipped classroom model on the academic success and 21st century skills of middle school students in the unit of systems in our body. The study was conducted with 6th grade students studying in a state school in Istanbul. In the study, an applied study was conducted with two experimental groups (n=29) and one control group (n=18). The flipped classroom model was applied in experimental groups, and the control group was taught in accordance with the curriculum. In the study, a quasi-experimental design with a pre-test post-test control group was used, which is one of the quantitative research methods. The data of the study were obtained with the academic achievement test and the 21st century skills scale. According to the results obtained in the study, the academic success of the students differed significantly in the classes where the flipped classroom model was applied compared to the classes where the current curriculum was applied. In addition, it was determined that the flipped classroom model positively developed the 21st century skills of the students.