Supramolecular drug delivery systems (DDS) are widely used in pharmacology during last decades for designing new preparations with improved properties. Most of fundamental and applied research in this field has been devoted to the inclusion complexes with cyclodextrins (CD), which are assumed to possess protective properties and to decrease the hydrophobic behavior of the included molecules. At present a new generation of DDS has been developing. Novel DDS are focused simultaneously on several purposes, including improved bioavailability and stability of drugs, targeted drug delivery, and enhanced activity. One of the compounds that appear to be promising is glycyrrhizic acid (or glycyrrhizin). A number of experimental facts of high therapeutic activity of glycyrrhizin conjugates have been published, but no understanding “how it works” was presented. This manuscript will highlight our attempts to answer this question using physicochemical approach, and also outline the challenges and future opportunities for medical applications of glycyrrhizin conjugates.