The intercalation of L-DOPA into the interlayer space of saponite, a 2:1 phyllosilicate, and the nature of host−guest interactions are investigated by a combined experimental and theoretical approach. L-DOPA zwitterions are accommodated vertically in the interlayer region as a bilayer of partially interdigitated species. The hydration state of the nanocomposite as well as the interaction geometry of L-DOPA molecules in the clay interlayer, are determined by periodic DFT calculations and found to be in agreement with experimentally obtained data. New insights into the transport properties for biomolecules in saponite are discussed.