A novel peptide, Cys-Trp-Cys (CWC), which firstly isolated from Guojing Baijiu was qualitative and quantitative studied by high-performance liquid chromatography and quadrupole-time-of-flight-mass spectrometry (HPLC- Q-TOF-MS) with a concentration of 11.06 ± 0.34 μg/L (P > 0.05). The antioxidant activity of the peptide was evaluated by the HepG2 cell model induced by 2, 2′-azobis (2-methyl propanimidamidine) dihydrochloride (AAPH) and in vitro chemical assays, including (1,1-diphenyl- 2-picrylhydrazyl radical 2,2-diphenyl- 1-(2,4,6-trinitrophenyl) hydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzthiazoline- 6-sulphonate) (ABTS), oxygen radical absorbance capacity, reducing power, and metal chelation assays. The results showed that CWC exhibited stronger antioxidant activity than Trolox in the ABTS assay. Furthermore, CWC inhibited AAPH-induced oxidative stress in HepG2 cells with a dose-dependent manner. Pretreatment of the cells with CWC (1, 2, and 4 mg/mL) caused the strong scavenging activities on the intracellular reactive oxygen species and a marked decrease in the reduced malondialdehyde (MDA). In addition, pretreatment with CWC prevented significantly the activities decrease in glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) induced by AAPH. CWC had strong antioxidant activity mainly due to its Cys residue containing a thiol group (–SH). These findings indicated that CWC was a potent natural antioxidant in Baijiu, which would be important for deeply understanding the relationship between the health and Baijiu. [ABSTRACT FROM AUTHOR]