Liver fluke disease remains a critical public health issue in Southeast Asia, driven by cultural dietary practices involving raw or undercooked freshwater fish. This study evaluates the impact of an interdisciplinary brain-based learning intervention aimed at increasing awareness and modifying dietary behaviors among early childhood students in Central Northeast Thailand. A quasi-experimental design was employed, involving 122 students from four provinces. The intervention incorporated brain-based learning activities such as storytelling, songs, and visual aids to enhance engagement. Pre- and post-tests, behavioral observations, and attitudinal surveys were conducted to assess the program’s effectiveness. Post-intervention results indicated significant improvements in knowledge about liver fluke transmission, symptoms, and prevention, alongside positive changes in behavior, such as increased avoidance of raw fish consumption and improved hygiene practices. Attitudinal surveys showed a shift in preferences toward safer eating habits. These findings suggest integrating brain-based learning with culturally relevant health education can foster sustainable behavior change in early childhood populations. Further research is recommended to explore this approach’s long-term impacts and scalability.