Toehold-mediated DNA strand displacement has emerged as a powerful tool in the construction of dynamic DNA nanostructures. In order to achieve fine and coarse control over displacement kinetics, a variety of toehold types including metallo-toeholds, photoactivated toeholds, remote toeholds, and allosteric toeholds, have been introduced by many research groups over the past two decades. This dissertation sheds light on the development of a novel strand displacement mechanism using high fidelity and orthogonal supramolecular host-guest interactions. DNA provides programmability, predictability, and self-assembly via Watson-Crick-Franklin base pairing, whereas supramolecular host-guest complexes provide solubility in aqueous media, bio-orthogonality, and directionality via reversible non-covalent binding. Taken together they provide smart building blocks to construct highly biocompatible, and versatile systems have potential applications in biomedical as well as material sciences. The first chapter of this dissertation describes the background and significance of DNA nanotechnology, with regard to various types of input responsive DNA devices. Here, toehold-mediated DNA strand displacement is described as a subsection of input responsive nucleic acids, followed by several examples of various toehold systems. Finally, the integration of supramolecular chemistry with DNA nanotechnology is discussed. The second chapter is focused on the development of host-guest interactions driven strand displacement strategy (termed as HG-TMSD), and modulation of displacement kinetics by varying the host-guest affinity. Furthermore, the third chapter entails two proof of concept applications governed by the HG-TMSD process: regulation of human carbonic anhydrase-II and development of a selective sensing platform for microRNA-182.