In bio‐medical field, one of the most challenging hurdles connected with development of therapeutics is the efficient transport and delivery of drugs to the infected cells of human body. Supramolecular chemistry provides innovative designs for effective biological applications such as drug and gene delivery. In various applications of supramolecular chemistry, macrocyclic molecules such as calixarenes, cyclodextrins, cucurbiturils, and pillar arenes serve as ideal hosts that can bind guest molecules based on the electron density and size of their cavities. This review focuses on the recent advancements in major supramolecular systems such as calixarenes (CA), curcurbiturils (CB), cyclodextrins (CD) and pillar[n] arenes (PAs). Owing to their non‐covalent interactions and adaptive capability, these supramolecular‐based nucleic acid delivery systems provide customized treatment options in cancer therapy. These supramolecular carriers are distinct due to their capacity to functionalize and alter their structure in accordance with the required application. The use of such amphiphilic macromolecules as a carrier for gene transfection have been thoroughly investigated leading to advancements in therapeutic research. The aim of this review is to highlight and showcase the endeavours of utilising supramolecular systems in drug/nucleic acid delivery.