Quantum dots with unique optical and chemical properties show great potential applications in biology and chemical and medical science. Nevertheless, their practical applications in various fields are greatly limited due to the presence of hydrophobic organic surfaces. In this paper, we report a simple and effective method based on ligand exchange and proton donor-receptor reaction to prepare ultrastable and amphiphilic quantum dots having bilayer ligands with ultidentate structure, which provide active sites for subsequent functional conjugation. Our results show that these quantum dots exhibit monodispersity, excellent stability and solvent-free fluidity. In addition, they maintain their optical properties in a chemical environment due to the large amount of amphiphilic amine salts as ligands, which also endow quantum dots with lower cytotoxicity and higher antibacterial activity. The synthesis strategy in this study provides a new insight into the design and fabrication of promising multifunctional materials for biology, medicine, and energy and display technologies.