Rice (Oryza sativa L.) is one of the most important food crops in China, and saline-alkali stress significantly affects the growth and development of rice. In this study, growth parameters were measured, and a metabolomics analysis technique was used to analyze differentially expressed metabolites in rice seedlings in response to saline-alkali stress. The results showed that growth, relative growth rate, and biomass of rice seedlings significantly decreased under saline-alkali stress. A total of 41 metabolites (16 up-regulated and 25 down-regulated) were significantly changed in leaves of rice seedlings under saline-alkali stress. There were 36 metabolic pathways associated with saline-alkali stress, of which starch and sucrose metabolism, glyoxylate and dicarboxylic metabolism, tricarboxylic acid cycle (TCA cycle), alanine, aspartate and glutamate metabolism, and pentose phosphate pathway were the most highly correlated. This study found that saline-alkali stress significantly reduced carbohydrate metabolism, respiratory metabolism, amino acid metabolism, and organic acid synthesis, while the increased amino acids may be the key metabolites for rice seedlings to adapt to saline-alkali stress. Our results provide new ideas for studying the metabolic mechanism of saline-alkali tolerance of rice seedlings