Interactions between DNA and adsorbed poly(l-lysine) (PLL) on liquid crystal (LC) droplets were investigated using polarizing optical microcopy and epi-fluorescence microscopy. Earlier, we demonstrated that adsorption of PLL to the LC/aqueous interface resulted in homeotropic orientation of the LC and thus exhibited a radial configuration of the LC confined within the droplets. Subsequent adsorption of DNA (single-stranded DNA/double-stranded DNA) at PLL-coated LC droplets was found to trigger an LC reorientation within the droplets, leading to preradial/bipolar configuration of those droplets. To our surprise, subsequent exposure of complementary ssDNA to ssDNA/adsorbed PLL-modified LC droplets did not cause the LC reorientation. This is likely due to the formation of polyplexes (DNA-PLL complex) as confirmed by fluorescence microscopy and atomic force microscopy. In addition, dsDNA-adsorbed PLL droplets have been found to be effectively useful to displace (controlled release) propidium iodide (a model drug) encapsulated within dsDNA over time. These observations suggest the potential for a label-free droplet-based LC detection system that can respond to DNA and may provide a simple method to develop DNA-based drug nanocarriers.