A hydroponic experiment was conducted to assess whether grafting with Cucurbita rootstocks could improve the salt tolerance of melon scions and to determine the physiological, biochemical, and nutritional responses induced by the rootstocks under salt stress. Two melon (Cucumis melo L.) cultivars (Citirex and Altinbas) were grafted onto two commercial Cucurbita rootstocks (Kardosa and Nun9075). Plants were grown in aerated nutrient solution under deep water culture (DWC) at two electrical conductivity (EC) levels (control at 1.5 dS m⁻¹ and salt at 8.0 dS m⁻¹). Hydroponic salt stress led to a significant reduction in shoot and root growths, leaf area, photosynthetic activity, and leaf chlorophyll and carotenoid contents of both grafted and nongrafted melons. Susceptible plants responded to salt stress by increasing leaf proline and malondialdehyde (MDA), ion leakage, and leaf Na⁺ and Cl⁻ contents. Statistically significant negative correlations existed between shoot dry biomass production and leaf proline (r = −0.89), leaf MDA (r = −0.85), leaf Na⁺ (r = −0.90), and leaf (r = 0.63) and root (r = −0.90) ion leakages under salt stress. Nongrafted Citirex tended to be more sensitive to salt stress than Altinbas. The Cucurbita rootstocks (Nun9075 and Kardosa) significantly improved growth and biomass production of grafted melons (scions) by inducing physiological (high leaf area and photosynthesis), biochemical (low leaf proline and MDA), and nutritional (low leaf Na⁺ and ion leakage and high K⁺ and Ca⁺⁺ contents) responses under salt stress. The highest growth performance was exhibited by the Citirex/Nun9075 and Citirex/Kardosa graft combinations. Both Cucurbita cultivars have high rootstock potential for melon, and their significant contributions to salt tolerance were closely associated with inducing physiological and biochemical responses of scions. These traits could be useful for the selection and breeding of salt-tolerant rootstocks for sustainable agriculture in the future.