The Internet and 5G era makes e-learning a vital part of modern education, and extensive evidence has shown that peer teaching and flipped classroom contribute to increased success in medical teaching. However, the applicability of these pedagogies in laboratory courses remains largely unexplored. This study aimed to evaluate the academic performance, proficiency in procedural skills, and perception of nursing students in physiology laboratory classes delivered with nontraditional classroom (NTC) pedagogies comprising the combination of e-learning, peer teaching, and flipped classroom. Each class was subdivided into two equal halves by successive student identification (ID) number and randomly assigned to the control or NTC group. Compared to the control class, NTC teaching significantly enhanced mean score of six preclass tests (67.77 ± 9.83 vs. 62.94 ± 9.70), with "B" graders increased obviously, suggesting that preclass e-learning was more effective than textbook-based preview, especially for general grasp of the topic. Similarly, average scores on postclass quizzes in the NTC group were improved (79.40 ± 9.12 vs. 74.43 ± 8.88). Lesser time cost and higher success rates were observed in trachea, artery, and heart catheterizations in the NTC group, although no disparities were found in ureteral intubation. The majority (~74%) of students supported the reform and shared positive experiences with NTC methodology. They reported that virtual experiments and self-paced procedural skill videos affected pre- and in-class learning outcomes most, respectively. These findings indicated that NTC pedagogy was workable to improve students' subject scores and proficiency in complicated and direct-viewing procedural skills and was favorable to students.