Liquid-liquid extraction (LLE) can be an effective strategy for the purification of polyphenols from a fermentation broth. However, solvents need to be chosen to ensure high extraction capacity and selectivity. For that purpose, a systematic study is here presented, where the partition of different polyphenols - naringin, naringenin, p-coumaric acid, and trans-resveratrol - was measured in different solvents and solvent mixtures and described using the semipredictive NRTL-SAC model. The minimum average absolute deviation obtained, based on predicted activity coefficients, was of 40%. With the exception of naringin, the NRTL-SAC molecular descriptors were estimated using solubility data already available in the literature. The obtained results made it possible to propose suitable LLE-based downstream process schemes for two possible purification scenarios: the recovery of trans-resveratrol and the purification of both naringenin and trans-resveratrol, two similar hydrophobic polyphenols, both from a fermentation broth containing hydrophilic impurities (e.g., sugars, proteins).