Drought stress negatively affects grapevine growth and development.  Grafting with rootstock is widely used to improve the quality of grape fruits and confer drought stress tolerance, but the underlying genetics and regulatory mechanisms are unclear.  Hence, we investigated the physiologic and transcriptomic profiles in the leaves of grafted SM/1103P (SM shoot/1103P root) and self-rooted SM (‘Shine Muscat’) as well as roots of grafted SM/1103P and self-rooted 1103P under drought stress conditions.  The results indicated that grafted grapevine effectively attenuated drought damage in grape leaves by increasing phytohormone levels and antioxidant enzyme activities, reducing H₂O₂ and MDA contents.  Transcriptomic profiling revealed a total of 11,855 and 11,197 differentially expressed genes (DEGs) were identified in grape leaves and roots respectively.  Weighted correlation network analysis (WGCNA) was performed based on the RNA-seq data, and five modules (greenyellow, black, turquoise, salmon and blue) were significantly correlated to drought stress.  Pathway analysis showed that DEGs were enriched in the plant hormone signal transduction and MAPK signaling pathway.  916 transcription factor genes (TFs) belonging to different gene families were detected that may participate in regulating the drought stress.  Quantitative real-time PCR (qRT-PCR) expression analysis of twelve drought stress responsive DEGs was used to verify the transcriptome data.  Furthermore, overexpression of VvMYBPA1 in Arabidopsis thaliana and grape callus tissues improved drought tolerance.  Our findings provided new insights into to the regulatory mechanism for improving grapevine adaptation to drought.