The objective of the present study was to identify peptides, based on active components of the red algae seaweed Pyropia yezoensis, able to inhibit the generation of reactive oxygen species (ROS), which is associated with aging and oxidative activities. Phycobilin, specific to red algae, covalently binds with water-soluble proteins. There are three types of pigment bound proteins, known as phycobiliproteins (PBPs): Phycoerythrin (PE), phycocyanin (PC) and allophycocyanin (APC). In the present study, PBPs reported previously to have antioxidant activities in P. yezoensis were identified and, based on these data, several peptides were synthesized (PBP 1-13) and their inhibition of ROS generation was examined. The existence of PBPs of each type, PE, PC and APC, was established in P. yezoensis and all were analyzed. In addition, PBP 1-2 and 7-9 peptides from PE were synthesized and showed antioxidant activities in HepG2 cells. In HepG2 cells, treatment with PBP2 reduced hydrogen peroxide-mediated oxidative stress and restored the expression of superoxide dismutase (SOD). Furthermore, phosphorylated nuclear factor erythroid-derived 2-like 2 (Nrf2) was elevated by PBP2 treatment. Overall, these results suggested that Nrf2-SOD pathways may be involved in the PBP2-mediated antioxidant effects. Therefore, from the investigations of P. yezoensis, several candidate peptides were identified with promising antioxidant and, potentially, anti-aging properties.