•Stronger ion-ion attraction in the procaine salicylate aqueous solution than in lidocaine salicylate.•Almost the same hydration number, but a significant difference in the organisation of water molecules around cations.•NH2 group attached to the procaine benzene ring significantly induce its hydrophilic properties.•Partially zwitter-ionic form of lidocaine amide group is better hydrated than the procaine ester group.•The tendency of cation-cation interactions between positively charged nitrogen and ester group in procaine. Ion-ion and ion–solvent interactions have been investigated in the aqueous solutions of two drug-based ionic liquids, lidocaine salicylate and procaine salicylate, from density, viscosity, molar conductivity and computational simulations studies. The density and viscosity results were fitted with the Masson and the Jones-Dole equations, respectively. Ultra-high accurate conductometric measurements were combined with the low-concentration chemical model to derive values of limiting molar conductivities, λo, limiting molar conductivity of the cations, λ+o, and association constants, KA, for examined ionic liquids at different temperatures. From the obtained thermodynamic parameters and the molecular dynamics study, stronger attraction between ions and slightly higher structure making ability in the aqueous solution of procaine salicylate was noted. A detailed insight into the ion’s interactions was analysed from the difference between the amide and ester functional group and the side groups attached to the benzene ring of cations. Based on the obtained results, the potential use of these ILs as transdermal local anaesthetic drugs was discussed.