Peptides and oligonucleotides are two of the most interesting molecular platforms for making bioactive materials. Peptides provide bioactivity that can mimic that of proteins, whereas oligonucleotides like DNA can be used as scaffolds to immobilize other molecules with nanoscale precision. In this Topical Review, we discuss covalent conjugates of peptides and DNA for creating bioactive materials that can interface with cells. In particular, we focus on two areas. The first is multivalent presentation of peptides on a DNA scaffold, both linear assemblies and more complex nanostructures. The second is the reversible tuning of the extracellular environment-like ligand presentation, stiffness, and hierarchical morphology-in peptide-DNA biomaterials. These examples highlight the potential for creating highly potent materials with benefits not possible with either molecule alone, and we outline a number of future directions and applications for peptide-DNA conjugates.