A critical challenge in the structural characterization of metal complexes in apolar environments is distinguishing transient structural isomers within an ensemble of lower- and higher-order assemblies. These structural variations arise from subtle changes in ligand architecture and metal coordination chemistry, which are often difficult to deconvolute. Here, we utilize ion activation in both drift-tube and cyclic ion mobility spectrometry-mass spectrometry (IMS-MS) to resolve ligand conformational isomerism and metal coordination isomerism in metal sandwich complexes of cyclic depsipeptide ligands known for selective metal ion transport. Our approach reveals that isomerism driven by ligand structural rearrangements exhibits low energy barriers, allowing their interconversion to be captured on the IMS-MS time scale. In contrast, isomers involving distinct metal coordination states are characterized by higher energy barriers, precluding rapid interconversion. These findings establish a direct correlation between isomer distributions and selective metal binding and transport, providing mechanistic insights into the biological functions of cyclic depsipeptides. This work underscores the utility of IMS-MS for disentangling complex structural dynamics in biologically relevant metal-peptide ligand systems.