Social innovation in mental health education is imperative in Japan. Mental health problems such as depression and anxiety disorders among Japanese children that may compromise their education and future occupational performances have become prevalent. Accordingly, the early prevention of mental health problems with cognitive-behavioral oriented Social and Emotional Learning (SEL) programs, which have mostly been developed in western countries, have been implemented. However, studies have revealed that cognitive-behavioral oriented programs tend to have limited efficacies within the Japanese context due to culturally unique challenges such as low confidence and time and resource constraints. Research in neuroscience has found that cognitive oriented top-down approaches that focus on cognitive change predominantly may not be developmentally appropriate for Japanese children. Consequently, the efficacy and feasibility of a neuroscience-informed child education (NICE) program was developed and examined in this study to address the demands of the Japanese school context by integrating neuroscientific perspectives into a cognitive-behavioral oriented school-based SEL program. Teachers and first-grade students (6–7 years old) were divided into two groups. In the program group, teachers conducted an eight-session NICE program during 20-minute after-class periods. In the information group, teachers applied the approach and skills in daily class management. While the students completed questionnaires regarding their class adjustment and social support awareness at three-time points, the teachers assessed students’ behaviors, including difficulties and prosocial behavior. The results supported the efficacy of the NICE program for promoting psychological well-being and increasing social support awareness and prosocial behaviors among Japanese students.