Updated project metadata. Mulberry (Morus alba) is a fast-growing perennial woody plant with a long cultivation history in China and a distribution throughout the country. To date, the molecular mechanism of mulberry response to abiotic stress is little known. In the present study, proteomics data were collected from the leaves of the mulberry cultivar Neo-Ichinose (Japan) under drought stress and analyzed. In total, 2871 proteins were quantified, among which 267 proteins were differentially expressed. A Gene Ontology enrichment analysis indicated that the molecular functions of the up-regulated proteins were mainly related to glutathione peroxidase activity, hydrolase activity, oxidoreductase activity, peroxidase activity and antioxidant activity. Protein domain enrichment analysis showed that the most important protein domains were associated with glutathione peroxidase, glycoside hydrolase, and chaperones. Additionally, a functional enrichment analysis demonstrated that the main metabolic pathways of mulberry seedlings in response to drought stress were arachidonic acid metabolism and glutathione metabolism, which were up-regulated, and chlorophyll and porphyrin metabolism and glycerol metabolism, which were down-regulated. Additionally, many proteins related to osmotic adjustment and stress signal transduction were evoked by drought. Taken together, these results suggested that redox control and osmotic adjustment mediated by multiple signaling pathways dominated the drought response of mulberry and that antioxidant proteins and enzymes, especially glutathione peroxidase, played vital roles in the redox rebalance of mulberry under stress.