China possesses abundant saline-alkali water resources that are currently underutilized. Developing saline-alkali water aquaculture could transform these abandoned resources into valuable assets and enhance fishery production. This study aimed to investigate the effects of acute alkalinity stress on the physiological metabolism of Eriocheir sinensis. A control group (0 mmol/L) and an alkalinity group (60 mmol/L) were established, with four treatment times (0, 6, 12, and 24 h) to examine the impacts of acute alkalinity stress on the mRNA expression of anti-stress and developmental regulatory genes (mTOR and AKT) in the hepatopancreas of E. sinensis, as well as antioxidant capacity indicators [catalase (CAT), total antioxidant capacity (T-AOC), malondialdehyde (MDA)] and muscle tissue structure, which are key tissues for energy metabolism. Results showed that after 6 h of alkalinity stress, AKT gene expression increased and then decreased, but remained significantly higher than the control group at 24 h (P<0.05). mTOR expression significantly increased after 6 h of stress (P<0.05) and remaind highly expressed. CAT enzyme activity in the hepatopancreas of E. sinensis significantly decreased after 6 h of stress (P < 0.05). T-AOC levels in the hepatopancreas significantly increased after 24 h of alkalinity stress (P<0.05), while MDA content significantly increased with prolonged stress, peaking at 24 h (P<0.05). Muscle tissue structure in E. sinensis was not significantly affected by 6 h of alkalinity stress. The observed increases in antioxidant enzyme activity (T-AOC) and upregulation of stress-resistant and developmental genes (AKT and mTOR) indicated that E. sinensis actively responded to alkalinity stress. This study provides theoretical guidance for eluciating the anti-stress mechanisms of E. sinensis in saline-alkali environments and for the future development of E. sinensis aquaculture.