The field of education continues to face the ongoing challenge of providing instruction that effectively addresses the diverse learning needs of students. In particular, teaching General Biology I presents unique complexities, as the subject requires not only factual knowledge but also a deep conceptual understanding of scientific principles. This study explores the use of Self-made Science Strategic Intervention Materials (S3IM) as a tool to enhance the cognitive domain of students, specifically targeting the least mastered learning competencies in General Biology I. The S3IM approach provides tailored, student-centered interventions that offer additional activities aimed at reinforcing understanding, promoting active engagement, and improving academic performance. Employing a Convergent Mixed Method Design, this research integrates both qualitative and quantitative data collection techniques, including surveys and interviews, to examine the effectiveness of the S3IM in enhancing students’ conceptual comprehension and learning outcomes. The study investigates how these self-designed materials influence student engagement, motivation, and academic achievement, while also exploring their adaptability to individual learning needs. By demonstrating the potential of innovative, self-created intervention resources, this research contributes to evidence-based strategies for addressing learning gaps in science education. The findings are expected to provide valuable insights for educators, curriculum developers, and policymakers seeking effective approaches to strengthen students’ cognitive skills and foster mastery in General Biology I.