Nucleic acids are highly integrated into molecular biology and exhibit very interesting character with immense engineering potential to improve human health and influence molecular biology. Consequently, these biopolymers are the quintessential material for facilitating natural and therapeutic functions in basic research, biomedicine, and biological sciences. The field of nucleic acid nanotechnology is a massive research endeavor to understand and take advantage of DNA and RNA. Progression of the field is evident with an increasing amount of therapeutic nucleic acids (TNAs) approved for clinical use and several TNAs (mRNA vaccines) proved to be highly efficient to address the SARS-CoV-2 pandemic. Nucleic acid nanoparticles (NANPs) are an innovative class of structures. Herein, a review of the field of nucleic acid nanotechnology is given to summarize the potential of the field. Then, a focus on NANPs is taken though experimental work that offers novel methods of restructuring and functional options. A novel assembly method via selective nuclease degradation of RNA/DNA hybrids is introduced and DNA templated silver nanoclusters, as a new class of therapeutics, are characterized to optimize their antibacterial function. These studies advance the development of functional nucleic acids for the treatment of diseases and the improvement of the quality of life.