Nigella sativa L. seeds are traditionally known for their ability to cure different diseases including airway disorders, back pain and chronic headache, paralysis, diabetes, hypertension, skin diseases, infection, and digestive system related disorders. Keeping in view the numerous traditional medicinal uses of N. sativa seeds which may be related to thymoquinone, the main component of its essential oil, we provide an overview of the biological efficacy and toxicology of thymoquinone to support their therapeutic potential in treatment of human diseases. The current review covers the recent literature from 2002 to 2021. The data was collected from books, journals, electronic searches (Pub Med, ScienceDirect, Google Scholar, and Springerlink), and theses. Thymoquinone exhibits importance in combating various diseases such as inflammation, arthritis, ulcerative colitis, cancer, neuropathic pain, male infertility, diabetes, hepatitis, cardiovascular, musculoskeletal, respiratory, renal, skin, viral and microbial infection, and neurodegenerative diseases comprising Parkinson's and Alzheimer's which explain the traditional uses of N. sativa seeds in folk remedies in curing different ailments.The current review provides an explanation of the ethnopharmacological uses of Nigella sativa L. seeds which is related to the pharmacological activities of thymoquinone. The pharmacological properties, pharmacokinetics, efficacy, high therapeutic index, lipophilicity, and safety margin make TQ a hopeful candidate for drug development.