Supplemental calcium application has been reported to alleviate the detrimental effect of NaCl-induced salinity on crop growth. Iso-molar solutions of NaCl and NaCl plus CaCl2 were used to study the osmotic and ionic effects of salinity on leaf dry biomass production and nutraceutical quality of cardoon (Cynara cardunculus L. var. altilis DC) grown in a floating system. A basic nutrient solution (control; T1) was enriched with 15 mm of NaCl + 10 mm of CaCl2 (T2), 30 mm of NaCl (T3), 30 mm of NaCl + 20 mm of CaCl2 (T4), or 60 mm of NaCl (T5). NaCl at 60 mm induced a 52% reduction of total leaf dry biomass compared with the control (T1); the iso-molar solution enriched with 20 mm of CaCl2 (T4) increased the total leaf dry biomass production in comparison with treatment containing NaCl at 60 mm (T5). Moreover, at moderate salinity (T2 and T3), the partial replacement of NaCl with 10 mm of CaCl2 (T2) in treatment containing 30 mm of NaCl did not help to reduce the adverse effect of NaCl on total leaf dry biomass production. Results of leaf mineral analysis demonstrated that the partial replacement of NaCl with CaCl2 reduced the accumulation of sodium and the nutrient imbalance. Nutrient solutions enriched with CaCl2 did not increase the accumulation of the osmoprotectant proline in leaves. Nutraceutical value of cardoon leaves was generally improved by saline treatments compared with the control. The regression analysis between phenolic compounds and antioxidant activity showed that total phenols and chlorogenic acid were the major determinants of antioxidant activity in cardoon leaf biomass. In conclusion, the partial replacement of NaCl with CaCl2 improved the leaf dry biomass production of cardoon only at the highest salinity levels with a limited effect on nutraceutical quality of leaves.