St. John’s Wort (SJW) has been intensively studied in the last years with respect to its pharmacological properties and to understand the mechanism of action of its bioactive compounds. In fact, it is currently used for the treatment of several disorders. Nevertheless, only recently nanotechnology has been applied for the delivery of SJW extract in vivo, to enhance its neuroprotective properties. In the present review, the advantages, the chemical characterization and the special biological features of SJW extract are discussed, underlining the potential use of nanotechnology in the development of drug carrier systems based on lipid nanoparticles. A special focus is given to solid lipid nanoparticles (SLN) and to nanostructured lipid carriers (NLC) given their versatility for a wide range of bioactive compounds.