Refractive materials found in the natural world often exhibit unique structures that result in intriguing physical properties and offer a valuable resource for designing tailored bio-inspired materials. Here, we investigate from first principles the factors that govern the refractive index of metal–amino-acid crystals. We specifically focus on the influence of crystal structure, metal ion inclusion, and spin configuration in phenylalanine- and cysteine-based materials. We find that the inclusion of copper and zinc metal ions in the crystal lattice has an important structural role that directly influences the refractive properties. In addition, the metal ions may contribute significantly to the dielectric response and therefore to the refractive index even within a given structure. Furthermore, in the synthetically available case of phenylalanine–copper we verify the results experimentally. Our results demonstrate the role of the inclusion of metal atoms in biogenic assemblies, emphasizing the potential use of this concept in bio-inspired molecular crystals that offer a flexible platform for the design of novel materials with desired optical features.