Aqueous Two-Phase Systems (ATPSs) based on choline salts represent a promising, environmentally friendly alternative to conventional liquid–liquid extraction methods due to their high water content, biocompatibility, and non-toxic nature. These characteristics make them particularly suitable for the recovery of active pharmaceutical ingredients (APIs), such as antibiotics and antipyretics, from contaminated water streams. The presence of pharmaceutical residues in aquatic environments has become a growing global concern, as these compounds are persistent and capable of inducing adverse effects on aquatic organisms, microbial ecosystems, and even human health. In this study, the liquid–liquid equilibria (LLE) of ATPSs composed of propan-1-ol, choline dihydrogen citrate ([Ch][H₂Cit]) or choline bicarbonate, and water were determined at 298.15 K and 0.1 MPa. The cloud-point method was used to estimate solubility curves, while tie-line compositions were established using third-degree polynomial correlations of electrical conductivity and liquid density data. The experimental tie-line compositions were accurately correlated using empirical models and successfully described using the electrolyte-Non-Random Two-Liquid (eNRTL) thermodynamic model. During thermodynamic modelling, non-randomness factors (α) for the solvents were derived from Density Functional Theory (DFT) calculations, with values of 0.1970 for propan-1-ol and 0.3333 for water. This approach reduced the number of adjustable parameters and enhanced the physical interpretability of the model. The studied systems demonstrated efficient extraction of salicylic acid, with partition coefficients (K) ranging from 2.1 ± 0.3 to 5.6 ± 0.9, confirming that ATPSs based on choline salts not only align with green chemistry principles but also provide a viable and sustainable strategy for the selective removal of pharmaceutical contaminants from polluted water streams. As water quality challenges intensify globally, the development of such eco-compatible separation systems is critical to promoting safer and more resilient aquatic environments.