In contemporary architectural discourse, light and color are recognized not merely as aesthetic elements but as dynamic design tools that play a crucial role in shaping users’ sensory and behavioral experiences within space. This study aims to develop an analytical–applied framework for employing light and color in the creation of human-centered architectural spaces in Iran, using a mixed-method approach that includes a systematic literature review, expert surveys, and case study analysis. In the first phase, a review of 48 scholarly articles led to the extraction of ten key influencing indicators. In the second phase, these indicators were prioritized by 20 experts in architecture and lighting design using a five-point Likert scale. The findings indicated that the indicators “impact on circadian rhythm” and “light intensity” received the highest rating (5 out of 5) from Iranian specialists. In the third phase, five prominent international and Iranian architectural projects were comparatively analyzed based on the high-priority indicators. The final results confirmed the alignment of optimal parameters with global standards and revealed that simultaneous consideration of critical qualitative factors—such as the non-visual effects of light and the psychology of color—within integrated design can play a key role in enhancing users’ health, well-being, and productivity. The proposed framework can serve as a practical guideline for architects and designers seeking to create human-centered, sustainable spaces that improve quality of life within the Iranian context.