Objective To explore and evaluate the effectiveness of the thematic experiential teaching model in a bioinformatics course. Methods An experimental control study was employed. From April to June 2022, 39 students majoring in 5-Year Basic Medicine from the Zhongshan School of Medicine at Sun Yat-sen University, from the classes of 2018 and 2019, were selected as the study subjects. The 26 students from the class of 2019 were assigned to the experimental group, which employed the ″thematic experiential″ teaching model, while the 13 students from the class of 2018 were assigned to the control group, which used traditional teaching methods. Course teaching satisfaction evaluation questionnaires and academic performance of students were used for assessment. The questionnaire was filled out anonymously and voluntarily by 34 participants Statistical analyses were conducted using Fisher's exact test and rank-sum test. Results The proportion of 21 students in the class of 2019 who evaluated the course teaching effect as ″excellent″ was 76.2% (16/21), significantly higher than 7.7% (1/13) observed among the students from the class of 2018. The proportion of 2019 class students who found the course ″very rewarding″ was 61.9% (13/21), significantly higher than the 2018 class students' 15.4% (2/13). The proportion of 2019 class students who ″strongly agreed″ to recommend the course was 61.9% (13/21), significantly higher than the 2018 class students' 7.7% (1/13). The median of final exam scores for the 2019 class students was 87 points, higher than the 2018 class students' 81 points. All differences were statistically significant (P<0.05). Conclusions Implementing the thematic experiential teaching model in a bioinformatics course helps to stimulate students' interest in learning and enhances teaching effectiveness and satisfaction.