The study aimed to measure the solubilities of L-serine and L-isoleucine in an aqueous ammonium sulfate [(NH4)2SO4] solution at different temperatures (288.15 to 308.15 K) using a gravimetric technique. In pure aqueous media L-serine solubility is 4.1218 in mol•kg−1 of water while for L-isoleucine is 0.3094 mol•kg−1 at 298.15 K. The obtained solubility data was used to estimate the thermodynamic properties of the amino acids, such as the standard Gibbs free energy and standard entropy change during the solvation process. The analysis involved investigating the short range chemical interactions between the amino acids and the electrolyte solution, which significantly influenced the solvation thermodynamics. The study found that L-serine exhibited a salting in effect, meaning its solubility increased in the presence of ammonium sulfate, while L-isoleucine experienced a salting out effect, resulting in decreased solubility with the electrolyte. Additionally, solubility parameters were employed to assess the chemical strength of the amino acids and understand their solute–solvent interactions and relative solubilities in the solution. Overall, this experimental investigation provided valuable insights into the solvation behavior and chemical characteristics of L-serine and L-isoleucine in the presence of an electrolyte solution.