We evaluate the potential in vitro cytotoxicity that may arise from metallic and magnetic DNA-templated nanostructures. By using a fluorescence-based assay, the viability of cells was examined after treatment with DNA-templated nanostructures. Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify the amount of nanoparticles internalized by the cells. Cell uptake of DNA-templated nanostructures was enhanced after encapsulating the nanostructure with layers of polyelectrolytes (PSS and PAH) mand targeting ligands. Transmission electron microscope (TEM) images provided evidence that the nanostructures were localized in vesicles in the cytoplasm of the cells. The results from this study suggest that gold, iron oxide, and cobalt iron oxide DNA-templated nanostructures do not induce in vitro toxicity.