Alcohol in water is one of the fundamental liquid–liquid solutions in chemical and biological processes. Water-alcohol mixtures exhibit many abnormal physicochemical properties, the origins of which remain mysterious. In addition, the presence of a high concentration of mesoscale objects in such mixtures has caused debate; many researchers attribute these objects to bulk nanobubbles because their concentration is strongly affected by the amount of dissolved air gases. To resolve these issues, here we use transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and atomic force microscopy (AFM) to study ethanol–water mixtures. TEM reveals mesoscopic clathrate structures with water molecules forming a crystalline matrix hosting a high density of tiny cells. The presence of these mesoscopic clathrate structures is further supported by a refractive index of 1.27 ± 0.02 at 405 nm measured via NTA and the hydrophilic nature of the mesoscopic structures implied by AFM observations, explaining many long-standing puzzles related to water-alcohol mixtures.