Platelet glycoprotein Ibalpha (GpIbalpha) interactions with von Willebrand factor (VWF) are a critical early event in platelet adhesion, which contributes to hemostasis and thrombosis. Here we report the structure of a complex between GpIbalpha and a potent peptide inhibitor. The cyclic peptide (CTERMALHNLC) was isolated from a cysteine-constrained phage display library, and in the complex this forms one and a half turns of an amphipathic alpha-helix, the curvature of which facilitates contacts with the curved concave face of the GpIbalpha leucine-rich repeats. The peptide has only limited overlap with the VWF binding site. It effectively inhibits by stabilizing an alternative alpha-helical conformation of a regulatory loop that forms an extended beta-hairpin upon VWF binding. The structure defines a previously unrecognized binding site within GpIbalpha and represents a clear strategy for developing antiplatelet agents targeting the GpIbalpha-VWF interaction allosterically.