<p>Mediterranean viticulture is increasingly affected by salinity since decades and it was necessary to develop new salt-tolerant varieties and rootstocks to ensure its productivity and sustainability. Among these alternatives, wild grapevine species, revealed to possess untapped genetic diversity and valuable traits that can be effectively utilized for grapevine varieties improvement. Until now, no work focused on the proteomic modifications in wild grapevine plants in response to salt stress. Here, we report a comparative physiological and proteomic analysis carried out on a salt-tolerant Tunisian wild grapevine (<i>Vitis vinifera</i> L. ssp. <i>sylvestris</i>), named "Tebaba", exposed to salt stress for more than two weeks. Physiological analyses demonstrated the ability of “Tebaba” accession to maintain its growth and photosynthetic activity along the salt stress period. The proteomic analysis revealed changes in many proteins associated with various molecular processes, including carbohydrate and energy metabolism, photosynthesis, stress response and defense, protein synthesis/processing/degradation, amino acids and nitrogen metabolism, signal transduction and secondary metabolites. The Tunisian wild grapevine accession "Tebaba" was able to preserve its physiological levels of growth and photosynthesis. It was able to stimulate its antioxidant activities and its Calvin cycle. Its salt tolerance was mainly expressed by a remobilization of energy, an up-regulation of the elongation factor, ubiquitin, and chaperone proteins, as well as an increase in amino acids. To our knowledge, this is the first proteomic study on the mechanisms of salt tolerance in wild grapevine (<i>Vitis sylvestris</i> L. ssp. <i>sylvestris</i>).</p>