Purpose <p>The repair of cleft lip is a highly intricate and challenging surgical procedure in plastic surgery. Consequently, it is also a pivotal and difficult subject in clinical education. Problem-based learning (PBL) is a student-centered teaching methodology that facilitates students in solving complex, practical, or real-world problems collaboratively. Given that the 3D-printed simulator features high-fidelity, multi-layer structures, including skin, muscle, and mucosa layers, we have incorporated it into the conventional PBL approach to address the limitations of traditional PBL in the teaching of cleft lip repair. The primary objective of this study is to investigate the application of the 3D-printed simulator in conjunction with PBL in the instruction of cleft lip repair and to enhance teaching quality.</p> Methods <p>A total of 40 senior stomatological undergraduates were randomly divided into two groups: the 3D-printed PBL group and the traditional PBL group (each group, <i>n</i> = 20). The 3D-printed group underwent instruction using the 3D-printed simulator in conjunction with the PBL teaching methodology, while the traditional PBL group utilized conventional teaching tools in conjunction with the PBL methodology. Subsequently, both groups of students were subjected to separate assessments to evaluate the outcomes, including theoretical examinations, operational assessments, and questionnaires.</p> Results <p>Compared with the traditional PBL group, the 3D-printed PBL group demonstrated significantly higher theoretical assessment scores (<i>P</i> &lt; 0.05). In operative skill evaluations, the 3D-printed PBL group outperformed the traditional PBL group in incision design, correction of columellar deformities, and upper lip symmetry restoration (<i>P</i> &lt; 0.001). Furthermore, the questionnaire results indicated a positive impact of the 3D-printed simulator combined with PBL on the learning experiences of stomatological undergraduates.</p> Conclusions <p>3D-printed simulators combined with PBL have proven to be highly effective in enhancing the educational outcomes for cleft lip repair courses.</p>