Recent advancements in the nanosciences offer a variety of low dimensional materials with precisely controlled and extremely attractive properties which range from improved mechanical strength to unique optical quality. In this Article, we exploit the unique optical properties of nanoscale ZnO materials in the enhanced fluorescence detection of interacting proteins using model biosystems including immunoglobulin G, bovine serum albumin, human serum albumin, streptavidin, and fibronectin. We also devise facile synthetic methods for direct growth of these ZnO nanomaterials in an array format in order to demonstrate their significant potential to serve in applications such as protein or peptide arrays. We demonstrate that the arrayed ZnO nanomaterials function as excellent fluorescence-enhancing substrates in the optical detection of interacting protein molecules without the need for any amplification. Benefited by the outstanding fluorescence-enhancing capability of nanoscale ZnO and its substantial potential for easy integration into biosensor arrays, our new approach may facilitate rapid, high-throughput, ultrasensitive, and specific protein detection that is much needed in the areas of basic biology and biomedical research as well as large-scale clinical testing and screening.