In the marine environment, salinity is one of the key factors affecting the survival, growth, maturation, and reproduction of shellfish, and their life activities are constantly influenced by the changes of salinity in the local marine environment. Research on the mechanisms of adaptation to salinity stress in marine shellfish has been an ongoing concern of scholars, and a large number of studies have shown that salinity stress affects biological processes such as growth and survival, osmotic adjustment, energy metabolism, and immune response of marine shellfish. In recent years and following the development and application of genomic and transcriptomic technologies, more and more studies have been conducted to explore the adaptation mechanism of marine shellfish to salinity stress at the molecular level. Therefore, this paper reviews studies on osmotic regulation, energy metabolism regulation, immune response, transcriptome and genome in the adaptation mechanism of marine shellfish to salinity stress, and then proposes the development potential of euryhaline shellfish in the field of saline alkali water. It can provide theoretical reference for the genetic breeding and healthy culture of marine shellfish.