The development of innovative drug delivery systems (DDSs) has advanced significantly in the area of nanomedicine during the last 10 years. Using DNA and RNA nanoparticles (NPs) as encapsulation vehicles for drug, proteins or genes, enabling controlled release of drugs is an efficient technique. The use of NPs of DNA and their possible uses in regulated drug release techniques are examined in this chapter. Scientists have developed NPs especially for drug delivery by taking advantage of the unique properties of DNA molecules, like their ability to self-assemble and compatibility with living things. When compared to traditional drug carriers, DNA NPs provide a number of advantages, including remarkable stability, easily customizable features, and scalable size and shape. By carefully planning their content and structure, researchers have been able to encapsulate many medicinal substances in a very effective manner. This development makes it possible to distribute medications precisely. There are significant benefits to adding medications, proteins or genes to DNA nanoparticles in relation to increasing therapeutic efficacy and lowering side effects. The encapsulated payloads are shielded by DNA NPs, which prolongs their time in the body and stops them from degrading. For sensitive biologics, including gene or protein treatments, which could be susceptible to enzymatic breakdown or rapid removal, the protective effect is particularly crucial. Additionally, DNA NPs’ surface may be modified to enable targeted distribution to specific tissues or cells, increasing delivery accuracy. The ability of DNA NPs to control drug release kinetics is a major advantage. By adjusting the structure of DNA nanoparticles, researchers may control the release rate of the encapsulated payload, allowing for a controlled and extended drug delivery. For drugs with narrow therapeutic ranges or those that must be administered continuously to get the best possible therapeutic outcomes, this control is essential. Furthermore, DNA NPs may respond to environmental stimuli like changes in light, pH or temperature, which can start the payload’s release at certain times or places. The accuracy of drug release control is improved by this function. DNA nanoparticles possess a wide array of possible uses in the controlled release of drugs and biomolecules. Drugs, peptides, proteins, DNA, RNA and aptamers are only a few of the medicinal molecules that the NPs may convey. They have the potential to be used therapeutically to address a range of illnesses, including illnesses that spread, cancer and genetic abnormalities. DNA and RNA nanoparticles may also be used for targeted drug delivery, overcoming biological obstacles and the limitations of traditional administration of drug techniques.