Background: Globally, Diabetic mellitus is a rapidly progressing metabolic disorder and is becoming a worldwide concern with several complications and deaths every year. Despite conventional anti-diabetic drugs numerous kinds of research are going on to get the best cost-effective therapeutic agents with the least adverse effects for the management of diabetesand its complications. Nigella sativa is a spice with multi-effects on various disorders like anti-diabetic, anti-cancer, immune modulator, anti-microbial, anti-inflammatory, anti-spasmodic, relives pain, bronchodilator, hepato and renal protective, gastro-protective, anti-oxidant properties. Amongst all effects, the anti-diabetic properties remained a cornerstone and was explored. Anti-diabetic effect of N. sativa was due to the presence of Thymoquinone, a major constituent responsible for its effect. Since long ago, studies revealed that the active constituent thymoquinone had a significant reduction in fasting and post-prandial blood glucose levels (glycemic control), probably affecting the pancreatic β-cells, on insulin production and secretion; moreover, lipid profile was shown to be improved in both clinical and preclinical trials. However, there are not many studies on the exact dose to be administered for the therapeutic effect clinically. Conclusion: The current review investigated and emphasized the molecular mechanism of N.sativabased on the pre-clinical, clinical and toxicological evaluations. This aimed for the estimation of effective dose of N.sativa therapeutically for healthier out-turn.