Rational design of RNA ligands continues to be a formidable challenge, but the potential powerful applications in biology and medicine catapults it to the forefront of chemical research. Indeed, small molecule and macromolecular intervention are attractive approaches, but selectivity and cell permeability can be a hurdle. An alternative strategy is to use molecules of intermediate molecular weight that possess large enough surface area to maximize interaction with the RNA structure but are small enough to be cell-permeable. Herein, we report the discovery of nontoxic and cell-permeable branched peptide (BP) ligands that bind to TAR RNA in the low micromolar range from on-bead high-throughput screening of 4,096 compounds. TAR is a short RNA motif in the 5?-UTR of HIV-1 that is responsible for efficient generation of full RNA transcripts. We demonstrate that BPs are selective for the native TAR RNA structure and that "branching" in peptides provides multivalent interaction, which increases binding affinity to RNA.