Abiotic stresses, including drought, have been found to affect the growth and medicinal quality of numerous herbs. The proposed study aims to study the effects of different drought regimes on the metabolic profile, growth, ecophysiology, cellular antioxidants, and antioxidant potential of Nigella sativa (Black cumin) leaf. Forty-day-old seedlings of N. sativa were exposed to three regimes of drought (control, moderate and high) for a week. UPLC-MS/MS metabolic profile of the leaf reveals the presence of more than a hundred metabolites belonging to anthocyanins, chalcones, dihydro flavonoids, flavonoids, flavanols, flavones, flavonoid carbonoside, isoflavones, etc. Drought was found to alter the contents of identified metabolites. Drought stress-induced oxidative stress and increased production of hydrogen peroxide and superoxide anions. Physiological changes, activities of antioxidant enzymes, contents of antioxidants, and proline were significantly high under drought to protect against the low water regimes. Furthermore, stressed leaf extract had higher antioxidant potential. Thus, N. sativa leaf bears multiple metabolic pathways and can tolerate a higher degree of drought or osmotic stress.