To enhance the effectiveness of integrating online and offline teaching, 1545 clinical and preventive medicine students from 2019 to 2021 were randomly allocated to two groups, A and B. The curriculum was divided into two segments. Initially, two groups were established for the first segment, covering an introduction to Biomolecular and Material Metabolism. The group A adopted a teaching strategy incorporating "massive open online course + a Social Media platform (WeChat) + Project/Problem-Based Learning + Flipped classroom", integrating online and offline methods. The group B followed conventional teaching practices. In the second course segment, which included molecular biology and clinical biochemistry, the two groups had their instructional format switched. Comparative analysis of student satisfaction, learning attitudes, and academic performance between the groups was conducted. The satisfaction survey indicated that the group which adopted the online and offline mode outperformed the conventional teaching group in satisfaction rate, satisfaction scores, excellence rate, and total scores. While both groups exhibited an improvement in learning attitudes, the teaching reform group showed a significantly higher level of enhancement. Furthermore, the reform group achieved superior overall average scores, basic average scores, comprehensive average scores, and an increased rate of excellence compared to the conventional group. The results demonstrate that adopting a blended teaching model significantly improved instructional quality and positively influenced students' engagement and attitudes in biochemistry and molecular biology studies.