DNA nanostructures offer precise ligand control but lack in vivo stability. We developed a biodegradable hydrogel (thiolated hyaluronic acid/gelatin) to deliver multi-helical square block DNA nanostructures (SQBs). Unlike DNA-matrix gels, this "decoupled" system entraps SQBs as discrete particles in an Mg2+-rich environment to preserve structural integrity. Release kinetics are tunable via crosslinking density. In vitro, encapsulated SQBs maintained stability and extended macrophage uptake to 5 days. In vivo, the system sustained SQB presence for 10 days, far exceeding the 24-hour clearance of free SQBs. This versatile framework enables localized, long-term deployment of complex DNA therapeutics.