In the context of global warming, the accelerated evaporation of seawater will lead to a continuous expansion of saline-alkali land area. As an important economic freshwater crustacean, investigation on the mechanism of damage to Eriocheir sinensis (E. sinensis) under saline-alkali environment will provide a valuable precedent for understanding the detrimental effect of climate change on crustaceans. In this study, histopathological analysis and integrative omics analysis were employed to explore the injury mechanism on the cerebral nervous system of E. sinensis exposure to saline-alkali stress. Our findings revealed that under this stress E. sinensis exhibited behavioral disorders and damage to cerebral neurosecretory cells and key organelles. Additionally, several pathways related to detoxification metabolism, neurotransmitter synthesis, and antioxidant defense were significantly down-regulated. Collectively, these results show, for the first time, that saline-alkali stress can induce neurodegenerative disease-like symptoms in E. sinensis, and provide critical information for understanding the harmful effects of saline-alkali environments.