Our lab studies biological and soft matter systems using high pressure and X-ray techniques. A novel high pressure technique, called high pressure cryocooling, has been developed for biophysical and X-ray science. The method was primarily developed for crystal cryoprotection in macromolecular crystallography. In addition, the method was successfully applied to stabilize ligand–protein interactions, to study the pressure effect on the structure, and to entrap an intermediate enzymatic state. It was revealed that the underlying physics involves interesting phase behaviors of glassy water at low temperatures. Using the high pressure method, we will study the phase behaviors of glassy water, water-protein interactions, and protein functions and dynamics at cryogenic temperatures.