The study of solubility and chemical thermodynamics of amino acids in aqueous and binary mixture of solvents give us ideas on the behaviors of biomolecules in industrial complex solvent system. Thus, here we have measured solubilities of two isostructural amino acids L-serine and L-isoleucine in aqueous and binary electrolytes solutions of sodium chloride (NaCl) and potassium chloride (KCl) respectively. This study was carried out using analytical gravimetric method at temperature range 288.15 K to 308.15 K. The obtained experimental saturated solubility values were used to derive the thermodynamics of solutions free energies. The free energetics of solvation due to transfer were then determined and explained properly. Different thermophysical characteristics in aqueous electrolytes media were assessed and correlated. A variety of chemical processes, the solubility and stability of amino acids were also explained in terms of solute–solvent, solvent–solvent, and acid-base interactions. © 2023 Elsevier B.V.