Deoxyribonucleic acids (DNA) exhibit many predominant capabilities such as specific binding affinities, catalytic activities, and/or chemical stability. On the other hand, gold and silver nanomaterials (NMs) possess unique sizeand shape-dependence optical properties, large surface area, biocompatibility, and high stability. These properties have enabled the extensive use of DNA with gold or silver NMs in optical biosensors. DNA-conjugated gold nanoparticles have become most popular optical probes for various targets, with advantages of high sensitivity and selectivity. Fluorescent DNA-templated silver nanoclusters (DNA-Ag NCs) have features of molecule-like optical properties, easy preparation, and good biocompatibility. In this chapter, we highlight the synthesis of water-soluble DNA-functionalized gold and silver NMs, and their optical properties and applications in bioanalysis and cell imaging.