Transformation of a dense metal–organic framework (MOF) to a highly porous form can radically improve its applications in drug loading. In this study, an environmentally friendly synthesis of potassium acetate γ-cyclodextrin metal–organic framework (γ-CD-MOF) in water was identified as a dense crystal form. Importantly, the molecular arrangement of the dense γ-CD-MOF was confirmed by single crystal X-ray diffraction and other characterizations. If the dense γ-CD-MOF was directly dried after separation from the mother solution, it is incapable of loading a model drug. However, the fresh dense crystal could be transformed into a highly porous form by introducing ethanol. The crystal transformation was demonstrated by enhanced drug loading capability and characterizations of powder X-ray diffraction (PXRD), small-angle X-ray scattering (SAXS), and the N2 adsorption isotherm. In all, the crystal transformation from dense to highly porous form could significantly facilitate the applications of γ-CD-MOFs in drug loading and other potential fields.