The recent decades have seen a surge of new nanomaterials designed for efficient drug delivery. DNA nanotechnology has been developed to construct sophisticated 3D nanostructures and artificial molecular devices that can be operated at the nanoscale, giving rise to a variety of programmable functions and fascinating applications. In particular, DNA‐origami nanostructures feature rationally designed geometries and precise spatial addressability, as well as marked biocompatibility, thus providing a promising candidate for drug delivery. Here, the recent successful efforts to employ self‐assembled DNA‐origami nanostructures as drug‐delivery vehicles are summarized. The remaining challenges and open opportunities are also discussed. Structural DNA nanotechnology provides a biocompatible platform to construct customized nanocarriers. Recent developments of DNA‐origami‐based drug‐delivery systems are summarized. Multifunctional, highly tunable, and biologically amenable, DNA‐based nanomaterials will provide powerful strategies to understand and treat disease.