Hydroxyapatite (HA) is promising in various biomedical applications owing to its similar chemical composition, structure and properties to the inorganic component in natural hard tissues. Herein, we report a DNA-templated microwave-assisted hydrothermal strategy for the preparation of HA nanostructured materials. As a kind of natural biomacromolecule, DNA molecules open up a new way to the synthesis of HA nanostructured materials with well-defined structures and morphologies. The HA nanostructured materials with a nanosheet-assembled hierarchical structure and a HA nanorod ordered structure are successfully prepared. The important roles of DNA molecules and pH values in the formation of HA nanostructured materials are investigated, and a possible formation mechanism is proposed. The as-prepared HA nanostructured materials exhibit a relatively high adsorption ability for chicken immunoglobulin Y (IgY) protein and a sustained protein release behavior. The as-prepared HA nanostructured materials after loading the IgY protein show a high antimicrobial activity. Thus, the HA nanostructured materials prepared by the DNA-templated microwave hydrothermal method are promising for the applications in various areas such as the prevention and treatment of dental caries.