The selective adsorption of DMSO vapor on calixarene scaffold from a mixture consisting of either DMSO and water or DMSO and methanol was studied. Two calixarene-type scaffolds based on 4-chlorobenzaldehyde were obtained by reacting the aldehyde with either resorcinol or pyrogallol and characterized by various techniques including NMR, FTIR, thermal, and XRD. These materials were then used as sorbent materials for separating vapors. Results from this investigation indicate the scaffolds show selectivity towards DMSO. The resorcinol-based scaffold showed a higher selectivity for DMSO compared to the pyrogallol counterpart. The influence of synthesis solvent on the conformation and structural changes resulting from the interaction of the guest molecules with the host was also investigated.