The loss of fetal membrane (FM) integrity and function in early pregnancy can have devastating consequences for the fetus and the newborn. However, the current fragmentary knowledge of FM biology has largely hampered the development of preventive FM sealing and healing strategies. Here, by an optimized protein sample preparation and offline fractionation before LC-MS/MS analysis we present an exhaustive human term amnion proteome characterization. The more than 5000 identified proteins greatly outnumbered previous reports. A Gene-Set Enrichment Analysis (GSEA) depicted ‘extracellular matrix’ and ‘cell-substrate junction‘ as two significantly enriched categories. Therefore, protein-protein interaction plots using these categories enabled the establishment of novel potential amniotic membrane cell-to-ECM interactions. Together, this thorough human amnion proteome, additionally to providing a basis for the study of compromised and preterm ruptured fetal membranes, could be a stepping-stone for the development of novel healing-inducing biomaterials.