Diabetes mellitus (DM) causes the change in the components of the plasma, which may induce tissue and organ injuries, including the heart and kidney. In the diabetic model db/db mice, intravenous injection of purified dipeptidyl peptidase III (DPPIII) attenuated the heart and kidney damages provoked by DM without alteration in blood glucose level. This led us to hypothesize that there might be peptide(s) that are involved in the progression of the DM-mediated damages and are cleaved by DPPIII. To explore the peptides, the whole peptidomics analysis (shotgun peptidomics) was conducted using tandem mass spectrometry, in which peptides derived from the plasma of PBS-infused C57BL/6 mice, PBS-infused db/db mice, and DPPIII-treated db/db mice were compared. The raw mass spectrometry data were deposited to the ProteomeXchange with the dataset identifier PXD025440. Together with the mass spectrometry analysis and other experiments, we identified a peptide named Peptide 2 (AA sequence: RLLWENGNL) as a substrate of DPPIII. Peptide 2 is a part of C3f (53% identical), and C3f can act as an anaphylatoxin like C3a. To quantify the amount in plasma derived from the plasma of PBS-infused C57BL/6 mice, PBS-infused db/db mice, and DPPIII-treated db/db mice, selected reaction monitoring (SRM) assay was performed. All of the chromatograms and quantified data obtained by SRM from the three mouse groups were shown in the Analyst formated and PDF files.