Bullfrogs (Aquarana catesbeiana) are increasingly farmed for their high nutritional value and adaptability to intensive aquaculture systems. However, salinity stress due to environmental changes and habitat salinization poses a significant challenge for both wild and farmed bullfrogs. This study examines the physiological responses of juvenile bullfrogs to varying salinity levels (0, 2, 4, 6 ppt) to better understand their capacity for osmoregulation and adaptation to salinization. Juvenile bullfrogs underwent salinity treatments for one week, and various physiological parameters, including digestive enzyme activity, antioxidant enzyme activity, and serum biochemical indicators, were measured. The study revealed that moderate salinity (2–4 ppt) enhanced pepsin and amylase activity while maintaining high survival rates. However, higher salinity levels (6 ppt) impaired antioxidant defense mechanisms and liver tissue, increasing oxidative stress markers such as malondialdehyde (MDA). The results suggest that bullfrogs possess a degree of salt tolerance, which may predict their resilience to future landscape salinization driven by environmental changes. This research provides valuable insights into the osmoregulatory mechanisms of amphibians under salinity stress, addressing a critical gap in knowledge essential for both conservation and aquaculture management.