<p>Mud crab (<i>Scylla paramamosain</i>), an economically important euryhaline species, is facing challenges in low-salt saline-alkali water bodies. This study measured the antioxidant capacity and metabolic responses of the posterior gills of mud crabs to explore their adaptation to long-term cultivation in chloride-dominated low-salt saline-alkali water. For mud crabs in low salinity (LS) group, the results showed lower total antioxidant capacity (T-AOC) concentration as well as low superoxide dismutase (SOD) and catalase (CAT) activities in posterior gills, and higher MDA concentration in both posterior gills and serum. Conversely, LS showed higher T-AOC concentration, as well as higher SOD and CAT activities in serum than control group (CK). One hundred and ninety-four (194) metabolites with differential expressions were observed among the 3910 metabolites, while 66 metabolites were up-regulated and 128 metabolites were down-regulated. Nine of the 43 metabolic pathways found by KEGG enrichment analysis were significantly impacted. Glycerophospholipids, organic oxidants, and carboxylic acids and their derivatives were increased in the posterior gills of mud crabs under chloride-type low-salt saline stress, while the amounts of trigonelline, betaine, and organic acids such as phosphoenolpyruvate decreased. Fumaric acid and pantothenic acid levels increased, while the TCA cycle, coenzyme A, and pantothenic acid biosynthesis were also markedly upregulated. According to these results, glycerophospholipid metabolism is essential for preserving posterior gill tissue adaption, while taurine, free amino acids, and betaine are osmotic regulators that help crabs adjust to low-salt saline-alkali stress. Energy metabolism of crabs living in complex chloride-type low-salt saline water depends on the TCA cycle and the differentially-expressed metabolites D-fructose, fumaric acid, and pantothenic acid. This work offers theoretical insights for farming mud crabs in low-salt saline-alkaline waters.</p>