We have obtained robust peptide-capped quantum dots (QDs) using a facile approach. The pentapeptide Cys-Ala-Leu-Asn-Asn (CALNN) is involved as the capping ligand, forming a self-assembly monolayer on the surface of QDs, and solubilization of hydrophobic QDs in water is realized by simply mixing with the ligands in sodium hydroxide solution. All of the characterization results show that the prepared small-sized QDs have excellent stability in acidic and high salt solutions. Additionally, the protein-mimicking surface property of the peptide-capped QDs eliminates the nonspecific cellular interaction, which in combination with the low cytotoxicity promises an ideal biomaterial in the future. Further functionalization and achievement of fluorescence resonance energy transfer (FRET) to graphene also display great potential for analytical applications.