A physiology laboratory course plays an important role in improving the scientific abilities of medical students. This study involved a teaching reform based on problem-based self-designed experiments in a physiology laboratory course. The study subjects were divided into two groups, i.e., students enrolled in 2019 were assigned to the traditional course control group (n = 146) and students enrolled in 2021 were assigned to the improved course test group (n = 128). Students in the test group were required to conduct self-designed experiments based on the questions for each experimental theme, in addition to completing the specified experimental items. At the end of the course, the differences in academic achievements between the two groups were compared. The results showed that compared to the control group, the students in the test group spent less time finishing the specified experimental items (P < 0.05). More students in the test group obtained good results in the operation assessment for the specified experiments (P < 0.05), and a significant increase in the number of winners in discipline-wise competitions, participants in scientific research projects, and academic publications was observed in the test group. Most of the students in the test group agreed that the self-designed experiment promoted their scientific thinking, helped them better understand theoretical knowledge, and improved their hands-on operation and team cooperation abilities. Our research showed that our teaching reform promoted students' self-directed learning and problem-solving abilities, stimulated their enthusiasm for scientific research, and was conducive to the cultivation of innovative medical talents.