Guanidinium organodisulfonates form lamellar host lattices in which adjacent two-dimensional hydrogen-bonded sheets consisting of topologically complementary guanidinium cations (G) and sulfonate moieties (S) are connected by the organodisulfonates, which serve as pillars that support inclusion cavities, between the sheets, which are occupied by guest molecules. Inelastic neutron scattering (INS) at low energies (35120 meV or 280-970 cm(-1)) has been performed to probe the lattice dynamics of selected GS inclusion compounds. The pillars and the guests can be easily interchanged to produce inclusion compounds with various host-guest compositions, which can have different solid-state architectures but with retention of lamellar character. The specific host-guest combinations were chosen to evaluate the influence of the host environment on the vibrational modes of the guests, with particular attention paid to the role of pillar-guest isomorphism and lattice architecture. The multicomponent character of these materials enables selective isotopic labeling (hydrogen or deuterium) of the components-guanidinium ion, organodisulfonate pillar, and guest molecule-so that specific features in the INS spectra of the inclusion compounds can be assigned unambiguously to each component. These assignments are corroborated by ab initio density functional theory calculations for free, isolated guest molecules, which also define the specific molecular motions associated with each feature in the INS data. The INS spectra produced by the ab initio calculations are in excellent agreement with the experimental data, illustrating the accuracy of the assignments while also demonstrating the reliability of the calculations for predicting INS spectra and lattice dynamics. Overall, the contributions to the INS spectra from the guest molecules do not differ appreciably from those observed for crystals of the pure guests or predicted by ab initio calculations. This demonstrates that the host lattices examined here do not appreciably influence the dynamic behavior of the guest molecules, most likely reflecting the absence of strong host-guest interactions, specifically between the organodisulfonate pillars and the guests.