MALDI-TOF MS is useful for the analysis of biomolecules. However, it is generally difficult to use MALDI-TOF MS for the analysis of small molecules (m/z <500 Da). This is in part due to the poor ionization efficiency for lack of high-proton-affinity functional groups and the presence of matrix-related ions in the low-mass range. We developed new labeling reagents containing C60 moiety to improve the ionization efficiency and to shift a mass of small molecules. We demonstrated the derivatization of amino acids and peptides by C60 derivatives and analyzed the derivatized by MALDI-TOF MS. As expected, the ionization efficiency of peptides was improved by coupled with C60 moiety. And by using the isotope-coded light (d0) and heavy (d5) reagents, relative quantification of amino acid was achieved. Our derivatization method is found to be useful for the qualitative and quantitative MALDI analysis of small molecules.