Abstract: Triploid oysters are widely cultured due to their superior growth compared to diploids. However, differences in temperature-salinity adaptation between di- and triploid oysters remain inconclusive. This study compared the survival rates, antioxidant enzyme activities, and gene expressions in di- and triploid Pacific oyster Crassostrea gigas cultured in different temperatures (17, 20, 23, 26, and 29 °C) and salinities (18, 22, 26, 30, and 34). Results showed that the optimum survival condition for both di- and triploids is 23 °C/30. At 23 °C, triploids exhibited significantly higher superoxide dismutase activity and lower heat shock protein 70 (Hsp70) expression than diploids. At 29 °C, triploids exhibited significantly higher survival rates than diploids. Across varying temperatures, triploids demonstrated significantly higher survival rates and antioxidant enzyme activities, along with lower malondialdehyde (MDA) levels and Hsp70 expression compared to diploids. The overall results demonstrate that triploids have a more robust antioxidant capacity, reduced oxidative damage, and lower mortality than diploids under temperature treatments. Additionally, at a salinity of 18, triploids showed significantly higher catalase (CAT) level than diploids. Across varying salinities, triploids maintained lower MDA levels. These results suggest that triploids possess a stronger antioxidant defense under salinity treatments. In conclusion, triploid C. gigas demonstrates superior adaptation to diverse temperature and salinity conditions over diploids and are recommended for culture to improve oyster production.