In comparison to inorganic particles or lipid-based systems, which are conventional nanoscale drug carriers, DNA-based nanostructures could be more efficient candidates due to the high programmability of their sequence, the predictability of their interactions, their great stability in physiological environments, precisely controllability in design, delivery, release, and targeting, structural diversity, their capacity for high payloads, high biocompatibility, low cytotoxicity, biodegradability, and high bioavailability. They can be easily taken up by many types of cells by various methods such as the endocytosis pathway without transfection. They have the ability to effectively cross biological barriers and specifically target drug sites, minimizing non-specific effects. While DNA nanostructures are versatile with different therapeutic strategies, including immunotherapy, chemotherapy, phototherapy, and gene therapy, high levels of flexibility and modifiability, which are the intrinsic properties of the DNA, not only can help in the multi-functionalizing of the DNA nanomaterials with various ligands through different ways such as conjugation, encapsulation, intercalation, and loading, but also provide the feasible integration of diverse functional modules into DNAbased nanocarriers, allowing for real-time tracking, conditional responding, and controlled release. All of these mentioned benefits along with the inherent compatibility of DNA nanostructures with therapeutic oligonucleotide drugs , , , , , , make DNA nanotechnology a significant suitable approach to developing smart-stimuli responsive drug delivery systems that are not only responsive to physiological stimuli but also can behave logically. These nucleotide based nanostructures make the production of logical nanomachines and intelligent nanorobots feasible.