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Nanomaterial‐based fluorescence sensing systems with the advantages of sensitivity and selectivity have been popular for quantitation of various analytes, including biomolecules, metal ions, and organic molecules. Fluorescent carbon dots (C dots) and noble metal nanoclusters (MNCs) separately composed of few carbon and metal atoms have attracted considerable research interest in the past decade, mainly because of their biocompatibility, as well as ease in preparation and conjugation. This review briefly discusses simple and popular strategies for the preparation of C dots and MNCs. Their sensing applications in monitoring pH values, quantitation of metal ions, and small molecules are emphasized. Their future use in conjunction with portable microsystems such as array and microfluidic device to develop high‐throughput and sensitive sensing systems for on‐site analysis is also discussed.