Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been widely used in traditional Chinese and Japanese medicine since ancient times. However, only in the last decades has a novel and unusual property of the GA been discovered to form water-soluble, supramolecular complexes with a variety of lipophilic drugs. These complexes show significant advantages over other known delivery systems, in particular, due to strong pH sensitivity, the properties of GA self-associates. In the present study, a supramolecular complex formation of the hypotensive and antiarrhythmic drug nifedipine with GA has been studied at different pH values, corresponding to the different degrees of GA dissociation, including a fully dissociated state of GA. Both NMR experiments and molecular dynamics simulations demonstrate the existence of the nifedipine complex with GA at all dissociation states of GA. However, optical absorption experiments show the decrease of complex stability and solubility at pH > 6 when the GA molecule is fully deprotonated. It means the higher release rate of the drug in a neutral and basic environment compared with acid media. These results could form the basis of follow-up studies of GA self-associates as pH-controlled drug delivery systems.