In aquatic environments, alkali-saline stress represents a substantial non-biological threat, severely affecting the normal growth and development of fish. To cope with these pressures, fish may employ mechanisms of genetic and epigenetic variation to adapt to extreme environments. However, it remains unclear how these mechanisms interact in promoting population persistence under environmental heterogeneity. To investigate the potential genetic and epigenetic mechanisms underlying adaptation to extreme alkali-saline environments, we selected Amur ide (Leuciscus waleckii), a fish species inhabiting highly saline-alkali lakes in Inner Mongolia, China, and studied the roles of its genome and DNA methylation patterns in the context of extreme environmental conditions. Genomically, we assembled the Amur ide genome and compared it with genomes of individuals from non-alkaline populations, revealing fundamental differences in genes associated with ion transport, osmoregulation, and immune function. Epigenetically, using DNA methylation sequencing, we designed experiments involving indoor alkaline stress and freshwater recovery, targeting genes involved in immune function, arachidonic acid metabolism, and steroid metabolism pathways. However, adaptive regulatory mechanisms driven by genetic and epigenetic variations appear largely distinct, suggesting autonomous roles for epigenetic variations. This complements and independently contributes to the adaptation of Amur ide to extreme salt-alkali environments. In conclusion, our study provides novel insights into the molecular mechanisms of phenotypic plasticity, crucial for predicting species' adaptive potential in rapidly changing aquatic environments.