Here, a facile strategy has been developed for the synthesis of peptide-capped CdTe quantum dots (peptide–QDs) in an aqueous phase by the one-pot method. The capping ligand, a designed peptide, can form a self-assembled hydrophobic layer on the surface of QDs, which makes the peptide–QDs exhibit excellent stability in acidic and high salt solutions. The as-prepared peptide–QDs are of potential values in the applications of biosensing and bioimaging.