The quality and yields of Sorghum bicolor plants are seriously affected by saline-alkali conditions. NAC (NAM, ATAF, and CUC) transcription factors are plant specific and have various functions in plant development and response to various stresses. To investigate how GsNAC2 functions in sorghum responses to saline-alkali treatment, the characteristics of GsNAC2 were analysed by bioinformatics methods, and NaHCO3:Na2CO3 (5:1, 75 mM, pH 9.63) saline-alkali stress solution was applied when sorghum plants were 2 weeks old. The research results show that GsNAC2 belongs to the NAC gene family. GsNAC2 was significantly induced by saline-alkali treatment and strongly expressed in sorghum leaves. GsNAC2-overexpressing sorghum plants had increased plant height, dry weight, moisture content, root activity, leaf length, chlorophyll content, stomatal conductance, relative root activity, relative chlorophyll content, relative stomatal conductance, and relative transpiration rate after saline-alkali treatment. Lower H2O2 and O2− levels, relative permeability of the plasma membrane, and malondialdehyde (MDA) content were found in GsNAC2-overexpressing sorghum. In transcriptome analysis, clusters of orthologous groups (COG) analysis showed that a high proportion of differentially-expressed genes (DEGs) participated in defence mechanisms at each processing time, and 18 DEGs related to synthetic glutathione were obtained. Gene expression analysis revealed that key genes in glutathione biosynthesis pathways were upregulated. GR and GSH-Px activities were increased, and GSH accumulated more with the overexpression of GsNAC2 after saline-alkali treatment. Furthermore, these results suggest that GsNAC2 acts as a potentially important regulator in response to saline-alkali stress and may be used in molecular breeding to improve crop yields under adverse environmental conditions.