Sweet sorghum has strong stress resistance and is considered a promising energy crop. In the present study, the effects of salt on the membrane lipid metabolism of two sweet sorghum inbred lines (salt-tolerant M-81E and salt-sensitive Roma) were analyzed. After treatment with 150 mM NaCl, higher levels of fresh weight and chlorophyll fluorescence, as well as lower levels of malondialdehyde (MDA) were found in salt-tolerant M-81E. Concomitantly, 702 and 1339 differentially expression genes (DEGs) in M-81E and Roma were identified in response to salt stress. We determined that most DEGs were related to glycerophospholipid metabolism, glycerolipid metabolism, and other membrane lipid metabolisms. Under NaCl treatment, the expression of the membrane-associated phospholipase A1 was down-regulated at the transcriptional level, along with an increased content of phosphatidylcholine (PC) in both cultivars. The inhibition of triacylglycerol (TAG) mobilization in M-81E delayed salt-induced leaf senescence. Furthermore, enhanced levels of glycerol-3-phosphate acyltransferase (GPAT) expression contributed to improved salt resistance in M-81E. The results of this study demonstrate membrane the role of lipid regulation in mediating salt-defensive responses in sweet sorghum and expand our understanding of the relationship between changes in membrane lipid content and salt resistance.