Despite its 3D porous structure, the pharmaceutical applications of cyclodextrin based cross-linked polymers are limited due to their structural irregularities. To address this issue, a template-directed strategy is used to obtain cubic micro and nano cyclodextrin cross-linked polymer (CD-cubes) from cyclodextrin metal organic frameworks in this study. The well-organized γ-CDs in MOFs were crosslinked by diphenyl carbonate by a facile single step chemical reaction. Scanning electron microscopy and X-ray diffraction analysis revealed the almost perfect cubic shapes of the particles with a disordered internal structure. Contrarily to the non-crosslinked materials which immediately dissolved in water, the CD-cubes were remarkably stable after extensive washing with water. The CD-cubes possessed a mesoporous structure with pore size in the range of 2–4 nm and showed much higher BET surface and 8 times higher adsorption capacity for doxorubicin as compared to conventional cyclodextrin-sponges.