The study aimed to develop culture-based lessons in Biology 9, integrating indigenous medicinal plants and practices in Cagraray Island. These developed lessons were designed incorporating features of research results, problem-based approach, active learning, and culture- or context-based teaching. The accounts from eight folk healers revealed the abundance of indigenous medicinal plants and practices for treating wounds, hypertension, anemia, cough and colds, and asthma. These illnesses were used as springboard for the development of five culture-based lessons with entry points in the K-12 curriculum. Implemented to 45 Grade 9 learners for five consecutive days at Cawayan National High School, the culture-based lessons were found effective in developing learning outcomes like conceptual understanding, metacognition, science process skills, and cultural appreciation using quantitative data analysis (p < 0.05). Qualitative data also supported these findings through Focus-Group Discussion (FGD), journal entries, interviews, and observations. Educational philosophy for culture-based learning revealed the need to incorporate hands-on activities producing concrete evidences for culture-based learning. In general, the study concluded with the potentiality of using indigenous medicine as resources for culture-based lessons in biology. For further study, it is recommended to design and develop more studies about local medicinal plants so they can be integrated, as well as multiple cultural facets, to culture-based lessons.