<p>Positive academic experiences and self-efficacy are key factors for mental health, integration, and success in higher education. Although evidence suggests that neuroscience knowledge may enhance perceptions of efficacy in educational settings, its role in undergraduate academic development remains underexplored. The study aims to investigate the impact of a neuroscience-based educational intervention on the academic development of undergraduates, focusing on academic experiences, self-efficacy, and mental health. An online and asynchronous neuroscience-based intervention was implemented, and its impact was evaluated through an experimental and longitudinal design. The study involved 124 undergraduates (aged 18–29), divided into control (<i>n</i> = 62) and experimental group (<i>n</i> = 62). The Academic Experiences Questionnaire showed that the intervention positively impacted academic adaptation, strengthening study strategies and promoting personal well-being. The Higher Education Self-Efficacy Scale showed significant improvement in the experimental group in the perceived capacity of academic, academic regulation, proactive actions, and academic management dimensions. The Depression, Anxiety, and Stress Scale indicated that the intervention may have contributed to the reduction of anxiety and stress symptoms. Pedagogical effectiveness was confirmed by the increase in performance on the general neuroscience knowledge questionnaire and on the questionnaires for each module. Participants’ perception reinforced these findings: the Instructional Materials Motivation Survey recorded high levels of situational motivation, while the Distance Learning Reactions Scales showed high satisfaction indices. The findings suggest that exposure to a neuroscience-based intervention can function as a tool for improving self-efficacy, promoting positive academic experiences, and contributing to the improvement of students’ mental health.</p>