<p>This study investigates the volumetric and acoustic properties of the local anesthetic drug mexiletine hydrochloride in aqueous and aqueous NaCl media over a temperature range of <i>T</i> = (288.15–313.15)K. Volumetric and acoustic properties are essential for understanding solute–solute and solute–solvent interactions in solution. In this study, we measured the density and speed of sound for a binary aqueous solution of mexiletine hydrochloride in the concentration range of (0.01–0.15)&#xa0;mol·kg⁻¹ and a ternary aqueous solution containing a fixed concentration of 0.06&#xa0;mol·kg⁻¹ of sodium chloride as solvent. These data were used to calculate the apparent molar volume of the solute (<InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(V_{\phi }\)</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>V</mi> <mi>ϕ</mi> </msub> </math></EquationSource> </InlineEquation>), the isentropic compressibility (<i>κₛ</i>) of the solutions, and the apparent molar isentropic compressibility (<i>κ</i>_<i>φ</i>) of the solute concerning drug concentration. The variation in temperature data allowed us to calculate the apparent molar expansivity (<InlineEquation ID="IEq2"> <EquationSource Format="TEX">\(E_{\phi }\)</EquationSource> <EquationSource Format="MATHML"><math> <msub> <mi>E</mi> <mi>ϕ</mi> </msub> </math></EquationSource> </InlineEquation>) and limiting expansivity (<InlineEquation ID="IEq3"> <EquationSource Format="TEX">\(E_\phi^0\)</EquationSource> <EquationSource Format="MATHML"><math> <msubsup> <mi>E</mi> <mi>ϕ</mi> <mn>0</mn> </msubsup> </math></EquationSource> </InlineEquation>) in infinitely dilute solutions at selected temperatures. Hepler's constant provides insight into a structure-breaking ability through negative values. The favorable result implies that mexiletine hydrochloride, with negative values, promotes structure formation in water and aqueous NaCl solutions. The negative readings indicate that mexiletine hydrochloride is structurally unstable at this temperature. That mexiletine hydrochloride exhibits strong hydrophilic and ionic interactions, with negative compressibility values highlighting a robust hydration structure. The presence of NaCl enhances solvation and reduces compressibility, suggesting significant structural changes in the solvent. These findings provide critical insights into the physicochemical behavior of mexiletine hydrochloride in biologically relevant environments, contributing to its pharmaceutical and biochemical applications. The hydrophilic–ionic and hydrophilic–hydrophilic interactions present in the systems are used to explain the trends observed in parameter variation for both experimental and computational data. We also discuss the results regarding ion–solvent interactions in binary solutions and the effect of adding sodium chloride on these interactions.</p> Graphical Abstract <p></p>