Salinity and heavy metal stresses are a great hindrance to the germination and development of plants. Nickel (Ni) is an indispensable micronutrient for plants at low concentrations. However, the proficiency depends upon the plant types. Citrullus colocynth is a medicinal cucurbit weed. The contemporary target of the study is to appraise the influence of combined stresses by varying concentrations of sodium chloride and nickel chloride on germination, morphology, biochemical ions, and physiology of C. colocynth. Germination percentage, root length, shoot length, fresh weight, dry weight, number of leaves, Na+, K+, Ca++, Cl-, Ni+, chlorophyll a and b, proline, SOD and CAT of C. colocynth were measured with nine combined levels (100 mM NaCl + 50 uM NiCl2), (200 mM NaCl + 50 uM NiCl2), (400 mM NaCl + 50 uM NiCl2), (100 mM NaCl + 100 uM NiCl2), (200 mM NaCl +100 uM NiCl2), (400 mM NaCl +100 uM NiCl2), (100 mM NaCl + 200 uM NiCl2), (200 mM NaCl + 200 uM NiCl2) and (400 mM NaCl +200 uM NiCl2). This experiment was conceded out in a completely randomized design with four replications. Germination percentage, root length, shoot length, fresh weight, dry weight, and the number of leaves, K+, Ca++, chlorophyll a, and b decreased by increasing stress levels while Na+, Cl-, Ni+, Proline, SOD, and CAT increased with increasing stress levels. This species has a positive morpho-physiological response under low(100mM NaCl, 50 uM NiCl2) and moderate (200mM NaCl, 100 uM NiCl2) combinations of salt and heavy metals while tolerance was observed under high-stress levels(400mM NaCl, 200 uM NiCl2). It is concluded that this species can be recommended for phytoremdiation against combined salt and heavy metal stresses.