In response to external stimuli the α-D-glucose molecule extensively transforms its H-bonding pattern and conformation. High-pressure reverses the linear compressibility and changes the hierarchy of intermolecular interactions in crystalline α-D-glucose. At 5.40(2) GPa it undergoes an isostructural phase transition rearranging the OH⋯O hydrogen bonds, promoting the role of CH⋯O contacts and eliminating voids in the structure. Such monotonic and abrupt transformations may be characteristic of sugars and polysaccharides.