This study evaluated the effect of a plateau environment on the heart and liver oxidation state of Tibetan pigs (TPs) and DLY pigs through analyzing AMPK, p38 MAPK, and Nrf2 signaling pathways. Twelve 120-day-old TPs and twelve 120-day-old DLY pigs were randomly divided into two groups in a plateau environment for three weeks. Exposed to a plateau environment, TPs exhibited a lower (p < 0.05) malondialdehyde level but higher (p < 0.05) glutathione, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) activities in the liver and heart than those observed in DLY pigs. TPs also showed higher (p < 0.05) mRNA levels of SOD and GSH-Px in the liver and heart compared with those of DLY pigs. The TPs showed higher (p < 0.05) mRNA and protein levels of AMPK and Nrf2 in the liver and heart compared with those of DLY pigs. Furthermore, TPs showed higher (p < 0.05) mRNA and protein levels of p38 MAPK in the heart and higher mRNA levels of p38 MAPK in the liver compared with those of DLY pigs under a plateau environment. In summary, TPs possess a stronger antioxidant capacity in the heart and liver than that of DLY pigs in a plateau environment through AMPK/p38 MAPK/Nrf2-ARE signaling pathways.