Understanding solute–co-solute interactions in aqueous media is vital for elucidating biochemical stability, protein folding, and drug formulation behaviour. This study investigates the thermodynamic and acoustic behaviour of L-serine and L-leucine in aqueous potassium oxalate (KOX) solutions over a temperature range of (288.15–318.15) K and varying molal concentrations. Density data were utilized to determine important thermodynamic parameters such as the apparent molar volume ( \(V_{\varphi }\) ), limiting partial molar volume ( \(V_{\varphi }^{\text o}\) ), and partial molar volume of transfer ( \(\Delta V_{\varphi }^{\text o}\) ) which shed light on solvation characteristics and the volumetric changes resulting from solute–solvent interactions. Likewise, speed of sound measurements was employed to calculate the apparent molar isentropic compressibility ( \(K_{{\varphi},{\text{s}}}\) ) and the partial molar isentropic compressibility of transfer ( \(\Delta K_{{\varphi},{\text{s}}}^{\text{o}}\) ) revealing information about compressibility effects and structural modifications within the solution. Furthermore, these parameters were analysed to evaluate pair and triplet interaction coefficients, providing a quantitative assessment of solute–solute and solute–solvent interactions across different concentrations and temperatures. The results reveal that ion–hydrophilic and hydrophilic–hydrophobic interactions dominate the solution behaviour, with L-leucine exhibiting stronger structure-making effects compared to L-serine due to its greater hydrophobic character. Positive temperature coefficients of ( \(\Delta V_{\varphi }^{\text o}\) ) and negative coefficients of (Ks) suggest enhanced molecular association at higher temperatures. The calculated pair and triplet interaction coefficients further confirm cooperative solvation effects in KOX media. Overall, the findings provide new insights into amino acid–oxalate interactions, relevant to biophysical, pharmaceutical, and biochemical systems where solvation and molecular association play a critical role.