Abstract Desolvation processes, though common in self‐assembled biological structures, are rarely evidenced and utilized in the design of crystalline architectures. In this study, we introduce a novel approach using the [Mo 8 S 8 O 8 (OH) 8 (guest)] 2− complex, formed by the self‐condensation of four [Mo V 2 O 2 S 2 ] 2− fragments around a guest unit (Mo VI O 6 H 4 or oxalate), as a chaotropic scaffold for crystallizing hybrid organic‐inorganic systems with natural cyclodextrins. Our findings reveal that β‐cyclodextrin (β‐CD) facilitates the formation of host‐guest complexes, while α‐cyclodextrin (α‐CD) induces the formation of a Kagome‐type structure with significant voids. These new compounds were thoroughly characterized using X‐ray diffraction (both powder and single‐crystal), N 2 adsorption, elemental and thermogravimetric analysis. Additionally, solution studies using 1 H NMR titration and small‐angle X‐ray scattering (SAXS) demonstrated pre‐association of the building units in solution. These results enhance our understanding of the design principles for supramolecular structures composed of inorganic polyanions and cyclodextrins.