Sugar metabolism is among the most important metabolic processes in soybean; it not only affects growth and development, but also plays a role in drought resistance. As a plant biological regulator, exogenous melatonin is assumed to regulate sugar metabolism. Here, physiological and transcriptomic approaches were used to determine the effects of melatonin on physiological indices and key genes and pathways associated with soybean sugar metabolism under drought stress. In plants subjected to drought stress, melatonin treatment increased dry matter accumulation, reduced malondialdehyde content, and increased the content of metabolized sugars in leaves, thereby enhancing soybean yield. Transcriptome analysis revealed that the genes differentially expressed in plants subjected to melatonin treatment and drought stress were enriched in the KEGG "sucrose and starch metabolism" pathway related to glucose metabolism. Among the differentially expressed genes, we identified 12 significantly altered genes associated with glucose metabolism that played roles in regulating the activities of glucose metabolism-related enzymes. Collectively, our results indicated that melatonin can enhance the output of glucose metabolites and tolerance of soybean subjected to drought stress by regulating the genes associated with glucose metabolism and activation of the related enzymes. Our findings provide a detailed theoretical basis for analyzing the regulatory effects of melatonin on soybean sugar metabolism under conditions of drought stress.