Biostimulants are innovative tools for the modern vineyard management, especially in relation to the new challenges posed by climate change. These products can modulate vine physiology and improve biotic/abiotic stress tolerance, but their mechanisms of action are still unclear. The present work aims at investigating the effects of two vegetal-derived protein hydrolysates on water-stressed vines, clarifying the involved mechanisms of action. Potted vines of Vitis vinifera L. cv. Montepulciano were subjected to a progressive water-stress. Vines sprayed pre-veraison with ‘Trainer’ (PH1) and ‘Stimtide’ (PH2) were compared with untreated vines. Leaves were sampled to perform non-target analysis of leaf proteome and metabolome. Gas exchanges performances were measured after re-watering and, at harvest, vine productivity and fruit composition were evaluated. PH1 significantly up-regulated metabolites involved in plant growth regulations and promoted the delay of senescence. At leaf Ψ= −1.4 MPa, both biostimulants up-regulated 6 and 7 photosynthesis-related proteins, respectively. However, 5 days past re-watering, no effects were found on assimilation rates, but leaf transpiration was improved by both treatments, as compared to control. The two formulates did not change vine yield and bunch morphology, but significantly reduced grapes total soluble solids (−3.5°Brix) and pH (−6%). PH2 significantly increased grapes TA (+1.87 g/L). The two biostimulants did not significantly affect the grapes total anthocyanins or their phenolic profile. In conclusion, PH1 and PH2 produced deep changes in leaf proteome and metabolome that delayed physiological maturity and maintained higher acidity, with no negative effects on anthocyanins and phenolics. Considering the negative effects of warming trends, today affecting most of traditional and modern wine regions, protein hydrolysates can be considered valuable tools to improve fruit quality and vineyard sustainability.