In this book, the authors report the recent results on the influence of different parameters (such as surface hydration, hydrophobicity, solute effects, thermal stability, porosity, macromolecular crowding) on the protein conformation based on the design and the characterisation of nanoporous silica-based materials containing different functional groups (e.g., hydrophobic alkyl, phosphate and fluorinated groups). The enhancement of the protein folding owing the physical properties and microstructure of the host matrix induced by the nature of the functional groups and the siloxane network play a major role on the protein biological activity and therefore to the development efficient bionanodevices such as biocatalysts, sensors, drug delivery systems or implanted devices. This book enlightens the bioapplications of silica-based glasses prepared from functionalised organosilane precursors used to mimic and to understand the different factors that influencing the protein folding process.