We describe the unique behavior of long DNA molecules in a cell-sized confinement by using cell-sized water-in-oil droplets coated with a lipid layer. It is shown that DNA molecules exhibit specific localization on lipid membranes accompanied by conformational transitions depending on the spatial size of droplets as well as the chemical structure of lipids coating the droplets. Interestingly, such specific behavior of DNA molecules causes on/off switching of transcriptional activity. We demonstrate the effect of crowding by adapting various kinds of macromolecules with different electronic charges and flexibility. As recently reported, it is shown that gene expression is remarkably accelerated in cell-sized confinement. We theoretically discuss the abovementioned unique behavior of DNA molecules in a micro-confinement. Further study in comparison with the actual behavior of DNA molecules in a living cellular system is expected to be fruitful.