This study examines how neuroscience can inform Islamic Religious Education (IRE) to strengthen students’ spiritual intelligence and meaningful learning. The study employed library research with a qualitative-descriptive and integrative literature review approach, analyzing recent scholarly literature on educational neuroscience, brain-based learning, spiritual intelligence, meaningful learning, and Islamic education. The findings indicate that neuroscience-based IRE should not be understood as merely applying biological knowledge of the brain to religious instruction, but as an integrative pedagogical framework connecting cognition, emotion, attention, memory, motivation, reflection, spirituality, and moral action. The synthesis shows that meaningful religious learning becomes stronger when students connect new Islamic concepts with prior knowledge, emotionally relevant experiences, reflective activities, authentic problems, Qur’anic values, and real-life practices. Spiritual intelligence is strengthened through repeated opportunities for self-awareness, transcendental reflection, ethical decision-making, gratitude, empathy, worship, and meaning-making. The novelty of this study lies in proposing an integrative Neuroscience-Based Islamic Religious Education Framework that connects neurocognitive processes with Islamic spiritual formation rather than treating neuroscience and spirituality as separate domains. The framework emphasizes brain readiness, emotional engagement, meaningful construction, spiritual reflection, behavioral internalization, and continuous reflection as interconnected stages of IRE learning.