Antioxidant peptides have received a great deal of attention. However, only a few studies have been conducted on the antioxidant peptides originating from Baijiu. A total of 1490 features deemed potential short-chain peptides (the amino acid number between 2 and 4, SCPs) were screened and analyzed by a customized short-chain peptidomics approach in Feng-flavor Baijiu (FFB) during 14 years of aging, with an obvious discrepancy between FFB aged for 3 years and 6 years being observed. Thirty-nine characteristic SCPs in total were identified and accurately quantified by high-throughput parallel reaction monitoring-based synthetic standards, with the contents ranging from 0.16 to 279.33 μg L. Combined with the absorption, distribution, metabolism, excretion, and toxicity analysis model, PGRW, WK, SC, and PAW, four novel antioxidant peptides with high ABTS radical scavenging capacity, were obtained using a customized quantitative structure-activity relationship (QSAR) model based on a two terminal position numbering method, with satisfied coefficients of determination (R), internal cross-validated R (Q), and external R (Rpre) of 0.925, 0.808, and 0.665, respectively. Furthermore, these 4 antioxidant peptides could block the Keap-Nrf2 interaction and promote the accumulation of Nrf2 by molecular docking analysis, and the interaction energy between peptide PGRW and Keap1 was higher than that between epigallocatechin gallate and Keap1 based on CHARMm forced field. Overall, this study facilitated the discovery of functional peptides in Baijiu and the understanding of aging mechanisms.