Natural products have served as a rich source for drug discovery and development. In the last decade their fruitful integration in the drug discovery pipeline declined due to their reduced bioavailability, mainly attributed to their poor aqueous solubility. We have investigated the interactions of the natural products quercetin (QUE) and silibinin (SLB) with (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD). The complexation enabled amplification of the solubility of these natural products and in the same time retained their bioactivity.