BACKGROUND: Preferential crystallization is a common technique used in the purification of enantiomers, proving that crystallization may also be applied to the purification of very similar molecules by seeding the solution with the desired compound. Nonetheless, its application to other organic molecules is less widely documented in the literature. Knowing that chemically related polyphenols are generally co-produced by fermentation and their purification can be too expensive for their market value, this technique may contribute to developing a downstream process with less expensive steps. The goal of this work is to show the applicability of the preferential crystallization concept to the purification of similar polyphenols - naringenin and trans-resveratrol - with either single or coupled crystallizers. RESULTS: After developing the required crystallization kinetic models, an experiment using two coupled vessels was devised, where a 63% yield of naringenin and 44% yield of trans-resveratrol was obtained, with ≥98% purity in both cases. When the vessels were working independently, 81% of pure trans-resveratrol (started 60% pure) and 70% of pure naringenin (started 68% pure) were recovered. CONCLUSION: The experiments performed show the possibility of separately purifying two similar molecules (from 60% to roughly 100%) with promising yields, despite their similar solubility. This method, which can be significantly improved, might provide an economically attractive way for the production of low added value products.