Heme-binding proteins constitute a large family of catalytic and transport proteins. Their widespread presence as globins and as essential oxygen and electron transporters, along with their diverse enzymatic functions, have made them targets for protein design. Most previously reported designs involved the use of α-helical scaffolds, and natural peptides also exhibit a strong preference for these scaffolds. However, the reason for this preference is not well understood, in part because alternative protein designs, such as those with β-sheets or hairpins, are challenging to perform. Here, we report the computational design and experimental validation of a water-soluble heme-binding peptide, Pincer-1, composed of predominantly β-scaffold secondary structures. Such heme-binding proteins are rarely observed in nature, and by designing such a scaffold, we simultaneously increase the known fold-space of heme-binding proteins and expand the limits of computational design methods. For a β-scaffold, two tryptophan zipper β- hairpins sandwiching a heme molecule were linked through an N-terminal cysteine disulfide bond. β- hairpin orientations and residue selection was performed computationally. Heme binding was confirmed through absorbance experiments and surface plasmon resonance (SPR) experiments (KD = 730 ± 160 nM). Circular dichroism (CD) and nuclear magnetic resonance (NMR) experiments validated the β-hairpin topology of the designed peptide. Our results indicate that a helical scaffold is not essential for heme binding and reveal the first designed watersoluble, heme-binding β-hairpin peptide. This peptide could help expand the search for, and design space to, cytoplasmic heme-binding proteins.