Metal-organic framework nanosheets (MONs) are a class of two-dimensional materials that combine organic ligands with metal nodes. The modular structure of MONs enables systematic tuning of surface chemistry without changing the overall topology, while their crystalline nature affords a periodic array of recognition sites that promotes multidentate binding. Presentation of these functional groups on the surface of the nanosheets, rather than within the pores of a threedimensional metal-organic framework (MOF), removes any size limitations. Early generations of MON-based biosensors have typically involved fluorescence quenching of dye-labeled single-stranded DNA, functionalization with bioreceptors and nanozyme behavior. In these examples, much of the sensitivity and selectivity is conferred by other components, such as aptamers and antibodies, enzymes, nanoparticles or other two-dimensional materials. To the best of our knowledge, there are currently no studies investigating the interaction of specific sequences of amino acids with MONs, although several studies have investigated their interactions with their three-dimensional analogs, MOFs. Indeed, several MOFs are promising catalysts for the formation and cleavage of peptides, as well as the selective hydrolysis of proteins. Parac-Vogt and co-workers investigated the adsorption of a diverse range of dipeptides onto various Zr-based MOFs. Extensive screening revealed that affinity depended on hydrophobic, aromatic and cation-π interactions arising from the hydrophobic/aromatic nature of the linkers and cluster connectivity. However, the diversity of both MOFs and peptide sequences and the complexity of their interactions means that identifying strong-binding combinations for use as highly selective biomolecular recognition surfaces remains a formidable challenge.