<p>This study aims to develop an efficient method for the selective separation of 3-hydroxybutyrate and crotonic acid obtained from the alkaline degradation of poly-3-hydroxybutyrate. To achieve this objective, salting-out assisted liquid-liquid extraction (SALLE) was applied and optimized using response surface methodology. The principle of salting-out behavior allowed selective and effective separation of the desired substances from the hydrolyzed mixtures under elevated salt conditions in liquid-liquid extraction. The optimized conditions were pH 4.5, 29.2 wt% of ammonium sulfate, and ethyl acetate-to-water ratio of 1:2.95 (v/v), which increased the purity of 3-hydroxybutyrate from 66.3% to 99.9% through serial SALLE steps with overall recovery yield exceeding 99.9% quantified by HPLC. This low-energy, catalyst-free process enables the sustainable up-cycling of poly-3-hydroxybutyrate to reusable monomers, with potential applications in pharmaceuticals and broad applicability in the recycling of biodegradable polymers.</p>