ETHNOPHARMACOLOGICAL RELEVANCE: Nigella sativa (N. sativa) L. (Ranunculaceae), well known as black cumin, has been used as a herbal medicine that has a rich historical background. It has been traditionally and clinically used in the treatment of several diseases. Many reviews have investigated this valuable plant, but none of them focused on its clinical effects. Therefore, the aim of the present review is to provide a comprehensive report of clinical studies on N. sativa and some of its constituents. MATERIALS AND METHODS: Studies on the clinical effects of N. sativa and its main constituent, thymoquinone, which were published between 1979 and 2015, were searched using various databases. RESULTS AND DISCUSSION: During the last three decades, several in vivo and in vitro animal studies revealed the pharmacological properties of the plant, including its antioxidant, antibacterial, antiproliferative, proapoptotic, anti-inflammatory, and antiepileptic properties, and its effect on improvement in atherogenesis, endothelial dysfunction, glucose metabolism, lipid profile dysfunction, and prevention of hippocampus pyramidal cell loss. In clinical studies, antimicrobial, antioxidant, anti-inflammatory, antitumor, and antidiabetic properties as well as therapeutic effects on metabolic syndrome, and gastrointestinal, neuronal, cardiovascular, respiratory, urinary, and reproductive disorders were found in N. sativa and its constituents. CONCLUSION: Extensive basic and clinical studies on N. sativa seed powder, oil, extracts (aqueous, ethanolic, and methanolic), and thymoquinone showed valuable therapeutic effects on different disorders with a wide range of safe doses. However, there were some confounding factors in the reviewed clinical trials, and a few of them presented data about the phytochemical composition of the plant. Therefore, a more standard clinical trial with N. sativa supplementation is needed for the plant to be used as an inexpensive potential biological adjuvant therapy.