A review.The use of protein templates for controlled synthesis of inorganic nanostructures has gained considerable attention in multidisciplinary fields, including electronics, optics, energy, sensing, and biomedicine, owing to their biocompatibility and structural programmability.The possible synergistic combination of protein scaffolds (and other biomols./biopolymers) with metal nanoclusters (MNCs) has created new class of highly photoluminescent nanoprobes and nanodevices.In particular, applications of protein-coated MNCs for chemosensing or biosensing of cancer biomarkers, neurotransmitters, pathogenic microorganisms, biomols., pharmaceutical compounds, and immunoassays are discussed in detail herein.Fluorescence-based and multimodal mol. imaging, both in vitro and in vivo based on functional proteins are also covered.Furthermore, we discuss burgeoning growth of protein-coated MNCs (e.g., gold (Au) and silver (Ag) NCs) to develop synergistic nanotherapeutics with potential biomedical applications in chemotherapy, radiotherapy, photodynamic therapy (PDT), photothermal therapy (PTT), and antibacterial activity, as well as MNC-containing nanocomposites for enhanced bioimaging and controlled drug release.Overall, proposed review highlights recent progress, tech. challenges and new horizons in this field, and summarizes our understanding of how MNC properties interact with biol. function of protein scaffolds to develop synergistic nanotherapeutics towards clin. translation.