To explore the feasibility of developing fishery aquaculture in low salt water, this study compared and analyzed the desalination effect of Sinonovacula contricta under different domestication methods. In this experiment, three groups with different low-salt domestication methods were set up (group Da: isokinetic domestication group with salinity decreased by 3 per 48 h; Group Db: isokinetic domestication group with salinity decreased by 1.5 per 24 h; group Dc: segmented domestication group with salinity decreased by 3 per 48 h before 10 and salinity decreased by 1 per 24 h after 10) and undomesticated group (Ud: salinity 5), water salinity decreased from 20 to 5, and the desalination period was 10 d. The survival, oxygen consumption rate, ammonia nitrogen excretion rate, feeding rate and antioxidant enzyme activity of clams in each experimental group were measured. The results showed that the survival rate of S. contricta in all domesticated groups was significantly higher than that of undomesticated group (43%), and the survival rate of group Dc (86%) was the highest. The oxygen consumption rate and ammonia nitrogen excretion rate in group Dc were significantly lower than those in group Da and group Db. The feeding experiments showed the feeding rate of group Dc was significantly higher than group A and group B. S. constricta in group Dc showed the least fluctuation of activities of superoxide dismutase (SOD) and catalase (CAT). In brief, the segmented desalination mode with a lower desalination rate and gradually decreasing the desalination rate with the decrease of salinity had significant advantages, which provided a reference for the desalination culture of S. contricta in low-saline water.