Layered double hydroxides (LDHs), or so-called anionic clays, consist of cationic brucite-like layers and exchangeable interlayer anions. Because of their biocompatibility, some LDHs, such as Mg/Al, Zn/Al, Fe/Al and Li/Al-LDH, can be used as host materials for drug-LDH host–guest supramolecular structures. The anti-inflammatory drug fenbufen has been intercalated into layered double hydroxides for the first time by co-precipitation under a nitrogen atmosphere. The product has been characterized by powder X-ray diffraction (XRD), FT-IR spectroscopy, elemental analysis and thermogravimetry (TG) and shows an expanded LDH structure, indicating that the drug has been successfully intercalated into LDH. In addition, the dependence of the nature of the fenbufen intercalation process on conditions such as pH value and chemical composition of the host has been systematically investigated. The interlayer distance in the intercalated materials increases with increasing pH value, resulting from a change in the arrangement of interlayer anions from monolayer to interdigitated bilayer. Drug release characteristics of the pillared LDH materials were investigated by a dissolution test in a simulated intestinal fluid (buffer at pH 7.8). The results show that the drug release of supramolecular LDH materials was a slow process, especially in the case of Mg/Al intercalated materials, suggesting that these drug-inorganic hybrid materials can be used as an effective drug delivery system.