Nucleic acid nanostructures are highly effective nanomaterials for biomedical purposes owing to their inherent programmability, biocompatibility, and biodegradability. Nonetheless, their usability has been restricted by inefficient synthesis strategies and their susceptibility to degradation in physiological environments. To beat these challenges, rolling circle replication (RCR), an isothermal enzymatic response, has emerged as a polymerization technique to generate ultra-long nucleic acid nanostructures with improved productiveness, biostability, and performance. This minireview offers a common overview of the versatile organic features and engineering methods for RCR based mostly nucleic acid nanostructures. We additionally spotlight latest advances in passive focused supply, lively focused supply, and stimulus responsive supply utilizing polymeric DNA and RNA nanostructures. Lastly, we define the present standing, key challenges, and future views of nucleic acid nanostructures for superior drug supply.