Intrinsically disordered proteins/regions (IDP/Rs), referring to highly dynamic proteins without any fixed structure, are often rich in charged residues, making them prone to electrostatic interactions. Upon binding, an IDP may either fold into a distinct structure, or stay disordered while bound to its ligand. In the case of the latter, binding may be detected using NMR, with the protein still giving rise to the narrow distribution of peaks in the proton dimension indicative of disorder. This heterogeneity and high degree of dynamics in binding is inclusive of very high affinity complexes, such as the interaction between prothymosin α and histone H1 (1). The extent to which heterogeneity and disorder can exist without the need for long-lived contacts, relying only on a mean-field type of interaction, is unknown. To address this, we selected an assortment of interacting protein pairs in which the ligand is disordered in its unbound state, and either stays disordered or adopts varying degrees of structure upon binding. Peptide ligands were synthesised using D-amino acids and compared to L-amino acid enantiomers, with the rationale being that if the interaction is truly electrostatically driven and disordered, a D-amino acid ligand should still bind with equal affinity and equal thermodynamics. We analysed the interactions using CD, ITC, and NMR methodologies, finding that disordered interactions can indeed occur regardless of the chirality of the ligand. Ligands that formed structure upon binding, however, were not able to interact with the same affinity when consisting of D-amino acids, with induced fit interactions unable to proceed with the D-amino acid ligand enantiomer. This is further evidence of the high-affinity, electrostatic, disordered interactions, and may be valuable for those designing peptide-based drugs to target disordered proteins.