Since the proposition of the Hofmeister series, guanidinium (Gdm) salts hold a special mention in protein science owing to their contrasting effect on protein(s) depending on the counteranion(s). For example, while GdmCl is known to act as a potential protein denaturant, Gdm2SO4 offers minimal effect on protein structure. Despite the fact that theoretical studies reckon the formation of ion-pairing to be responsible for such behavior, experimental validation of this hypothesis is still in sparse. In this study, we combine electrochemical impedance spectroscopy (EIS) and THz spectroscopy to underline the effect of GdmCl and Gdm2SO4 on a model amide molecule N-methylacetamide (NMA). Molecular dynamics (MD) simulation studies predict that Gdm2SO4 forms heteroion pairing in water, which inhibits Gdm+ ions to approach NMA molecules, while in case of GdmCl, Gdm+ ions directly interact with NMA. The …