Objective To compare the effectiveness of three teaching modes, namely traditional teaching, online teaching, and online and offline blended teaching, in the teaching of the clinical nutrition elective course, and to evaluate the advantages of the online and offline blended teaching mode. Methods A total of 316 students taking the clinical nutrition elective course at Sichuan University in one of the three semesters, Fall 2019-2020, Spring 2019-2020, and Fall 2020-2021, were enrolled as the study population. In the offline group, 69 students used the traditional teaching mode; in the online group, 133 students used the online teaching mode through Chaoxing Xuexitong application; in the online and offline blended teaching group, 144 students used the traditional teaching mode combined with the online teaching. The final exam results and questionnaire satisfaction of the three groups were analyzed and compared. The exam results were presented as median (lower quartile, upper quartile). Results The exam results of the online group [males: 88.0 (85.0, 93.0); females: 91.0 (86.0, 94.0)] and the online and offline blended group [males: 90.0 (83.0, 94.0); females: 91.0 (87.5, 95.0)] were significantly higher than those of the offline group [males: 83.0 (77.0, 89.0); females: 77.5 (67.0, 87.0)] (P<0.001). Compared to the offline teaching mode and online teaching mode, the female students’ satisfaction with the online and offline teaching mode was better (P<0.01). Conclusion The online and offline blended teaching mode can significantly improve students’ performance and learning motivation, and provide a basis for promoting the reform of the clinical nutrition elective course.