AbstractThe design of surface ligands is crucial for ligand‐protected gold nanoclusters (Au NCs). Besides providing good protection for Au NCs, the surface ligands also play the following two important roles: i) as the outermost layer of Au NCs, the ligands will directly interact with the exterior environment (e.g., solvents, molecules and cells) influencing Au NCs in various applications; and ii) the interfacial chemistry between ligands and gold atoms can determine the structures, as well as the physical and chemical properties of Au NCs. A delicate ligand design in Au NCs (or other metal NCs) needs to consider the covalent bonds between ligands and gold atoms (e.g., gold–sulfur (Au–S) and gold–phosphorus (Au–P) bond), the physics forces between ligands (e.g., hydrophobic and van der Waals forces), and the ionic forces between the functional groups of ligands (e.g., carboxylic (COOH) and amine group (NH2)); which form the underlying chemistry and discussion focus of this review article. Here, detailed discussions on the effects of surface ligands (e.g., thiolate, phosphine, and alkynyl ligands; or hydrophobic and hydrophilic ligands) on the synthesis, structures, and properties of Au NCs; highlighting the design principles in the surface engineering of Au NCs for diverse emerging applications, are provided.