Although melatonin was affirmed to alleviate drought stress in various plant species, the mechanism in kiwifruit remains to be elucidated. In this study, the transcriptomes of kiwifruit leaves under control (CK), DR (drought stress), and MTDR (drought plus melatonin) treatments were evaluated. After comparisons of the gene expression between DR and MTDR, the differentially expressed genes (DEGs) were screened. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated three significant pathways, which were mainly involved in the glutathione metabolism, ascorbate and aldarate metabolism, and carotenoid metabolism. Therefore, the content and metabolic gene expression level of ascorbic acid (AsA), glutathione, and carotenoid were higher in the MTDR treatment than that in others. Furthermore, the activity and mRNA expression level of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) were also promoted in the MTDR group. Combined with these results of important secondary metabolites and protective enzymes measured in the seedlings in different treatments, it could be concluded that exogenous melatonin induced the ascorbic acid-glutathione (AsA-GSH) cycle, carotenoid biosynthesis, and protective enzyme system to improve seedling growth. Our results contribute to the development of a practical method for kiwifruit against drought stress.