Natural enamel's exceptional hardness and fatigue resistance properties arises from its hierarchical structure of inorganic and organic phases. To understand this Structure–Functional relationship, bio-inspired structures have been developed using water-glass (WG) as the inorganic component alongside various polymers as the organic counterpart. WG with adjustable water content and viscoelastic behavior, enables to study how hydration affects mechanical properties and microstructure. By optimizing drying conditions and composite design in both 2D and 3D, our WG-polymer systems reveal the structure-property relationships critical for good fatigue performance. In addition, applied machine learning approaches were used to correlate hydration-dependent features with mechanical outcomes, providing predictive insights beyond experimental observation. This research provides insights into how hierarchical organization and hydration influence functionality, creating pathways for synthetic materials with enamel-inspired properties in biomedical applications.