Two novel peptides, ECH (Glu-Cys-His) and YECG (Tyr-Glu-Cys-Gly), were designed based on glutathione (Glu-Cys-Gly, GSH) and their antioxidant activities were studied. Various chemical methods based on single-electron-transfer (SET) and hydrogen-atom-transfer (HAT) were applied to evaluate the antioxidant activities of the peptides. For SET-based assay, tripeptide ECH displayed the highest DPPH radical scavenging activity (80.16%) and the strongest reducing power (A 700 =0.378). Besides, ECH also exhibited the best inhibition activity toward linoleic acid peroxidation with inhibition rate 98.25% at 7th day, which is a HAT-based assay. However, for another two HAT-based assays, it was tetrapeptide YECG that showed extraordinary oxygen radical absorption capacity (ORAC value=2.42μM Trolox/μM) and ABTS free radical scavenging ability (8.88mM Trolox/mM). In vitro cultured PC12 cell model also suggested that YECG gave the best protection for PC12 cells to resist H 2 O 2 -treated necrosis. It was found that the discrepancy of antioxidant capacity between ECH and YECG was caused by the presence of antioxidant amino acids (His/Tyr) and their position in peptide chain. With His located at C-terminal position, ECH demonstrated good electrons donating capacity, while with Tyr at N-terminal position, YECG exhibited strong oxygen radical absorbance capacity.