Salt stress is an important environmental limiting factor. Water dropwort (Oenanthe javanica) is an important vegetable in East Asia; however, its phenotypic and physiological response is poorly explored. For this purpose, 48 cultivars of water dropwort were grown hydroponically and treated with 0, 50, 100, and 200 mm NaCl for 14 days. Than their phenotypic responses were evaluated, afterward, physiological studies were carried out in selected sensitive and tolerant cultivars. In the present study, the potential tolerant (V11E0022) and sensitive (V11E0135) cultivars were selected by screening 48 cultivars based on their phenotype under four different levels of salt concentrations (0, 50, 100, and 200 mm). The results depicted that plant height, number of branches and leaves were less effected in V11E0022, and most severe reduction was observed in V11E0135 in comparison with others. Than the changes in biomass, ion contents, accumulation of reactive oxygen species, and activities of antioxidant enzymes and non-enzymatic antioxidants were determined in the leaves and roots of the selected cultivars. The potential tolerant cultivar (V11E0022) showed less reduction of water content and demonstrated low levels of Na+ uptake, malondialdehyde, and hydrogen peroxide (H2O2) in both leaves and roots. Moreover, the tolerant cultivar (V11E0022) showed high antioxidant activities of ascorbate peroxidase (APX), superoxide dismutase, peroxidase, catalase (CAT), reduced glutathione (GSH), and high accumulation of proline and soluble sugars compared to the sensitive cultivar (V11E0135). These results suggest the potential tolerance of V11E0022 cultivar against salt stress with low detrimental effects and a good antioxidant defense system. The observations also suggest good antioxidant capacity of water dropwort against salt stress. The findings of the present study also suggest that the number of branches and leaves, GSH, proline, soluble sugars, APX, and CAT could serve as the efficient markers for understanding the defense mechanisms of water dropwort under the conditions of salt stress.