Improving the stability of protein–mineral interfaces while preserving biological activity is a major challenge in biosensor and functional biomaterials design. Ancient tooth enamel offers a unique opportunity to identify protein sequences that have persisted in mineralized environments for millions of years. Here we investigate whether archaeological protein evidence can guide the selection of new peptide candidates for biomaterials engineering. We analyzed amelogenin (AMELX) peptide coverage from 12 ancient enamel specimens dating from approximately 0.4 to 2 million years ago. The data reveal, beyond the established C-terminal hydroxyapatite-binding region, two new peptides regions, archaeologically persistent regions (APR1 and APR2), with substantial archaeological coverage (82.7% and 100%, respectively) and different chemical and physicochemical properties from the C-tail, including differences in electrical charge, isoelectric point, and hydropathy. These findings identify additional AMELX sequences for investigating protein–mineral interactions and suggest that archaeological proteomics can guide the selection of new peptide motifs and candidate protein-mineral interfaces whose potential to improve biosensor durability can be evaluated experimentally.