The successful realization of thin film composite (TFC) organic solvent nanofiltration (OSN) membranes with high permeability and small solute selectivity for solute-solute separation to purify drugs in complex solution environments remains challenging in the pharmaceutical industry. Here, we present the preparation of high cross-linked TFC OSN membranes via interfacial polymerization (IP) utilizing phlorotannin, a plant-derived biomass phenolic compound, as a promising aqueous phase monomer. Benefiting from the presence of multiple cross-linking sites and twisted rigid structure in phlorotannin, nanofiltration membranes with excellent molecular selectivity and solvent permeability were successfully fabricated. This allowed for straightforward separation and purification of active pharmaceutical ingredients from intermediates. The membranes demonstrated remarkable stability over extended periods of operation and adaptability to a diverse array of solvent environments, making them a highly promising option for use in fine chemicals, biopharmaceuticals, and other fields.