Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) drives apoptosis selectively in cancer cells by clustering death receptors (DR4 and DR5). While it has excellent in vitro selectivity and toxicity, the TRAIL protein has a very low circulation half-life in vivo, which has hampered clinical development. Here, we developed core-cross-linked micelles that present multiple copies of a TRAIL-mimicking peptide at its surface. These micelles successfully induce apoptosis in a colon cancer cell line (COLO205) via DR4/5 clustering. Micelles with a peptide density of 15% (roughly 1 peptide/45 nm2) displayed the strongest activity with an IC50 value of 0.8 μM (relative to peptide), demonstrating that the precise spatial arrangement of ligands imparted by a protein such as a TRAIL may not be necessary for DR4/5/signaling and that a statistical network of monomeric ligands may suffice. As micelles have long circulation half-lives, we propose that this could provide a potential alternative drug to TRAIL and stimulate the use of micelles in other membrane receptor clustering networks.