Stilbenes, naturally occurring polyphenolic secondary metabolites, play a pivotal role in adaptation of various plant species to biotic and abiotic factors. Recently, increased attention has been directed toward their potential to enhance plant stress tolerance. We evaluated drought tolerance of three grapevine varieties grown with different levels of water deficit. Throughout, we studied physiological mechanisms associated with drought stress tolerance, particularly stilbene accumulation in root tissues, using HPLC. Additionally, we explored the possible relationship between antioxidant potential and stilbene accumulation in response to water deficit. The results underscore the detrimental impact of water deficit on grapevine growth, water status, and membrane stability index, while revealing varying tolerance among the studied genotypes. Notably, Syrah variety had superior drought tolerance, compared to Razegui and Muscat d'Italie grapes. Under severe water deficit, Syrah exhibited a substantial increase in levels of stilbenic compounds, such as t-resveratrol, t-piceatannol, t-ɛ-viniferin, and t-piceid, in root tissues compared to other genotypes. This increase was positively correlated with total antioxidant activity (TAA), emphasizing the active role of resveratrol and its derivatives in total antioxidant potential. This demonstratres the potential involvement of resveratrol and its derivatives in enhancing antioxidant status of the drought-tolerant Syrah grape variety. Our findings suggest that these stilbenes may function as valuable markers in grapevine breeding programs, offering novel insights for the sustainable cultivation of grapevines in water-limited environments.