The aim of this chapter is to review the ethnobotanical uses, chemical composition, and biological effects of Hyoscyamus niger. The plant has been known since the ancient era and the ethnobotanical records have indicated different uses including toothache, asthma, and gastrointestinal problems, as a sedative, hallucinogenic. Observed ethnobotanical uses could be explained by the presence of alkaloids, especially hyoscyamine, scopolamine, and atropine. In recent studies, some new compounds have been isolated as well as the alkaloids. In biological activity studies, we have observed different actions including antifungal, antibacterial, antidiarrheal, antisecretory, bronchodilator, and urinary bladder relaxant abilities. However, the plant is known as a toxic plant and different cases have been reported on poisoning with the plant. At this point, human beings have to be more careful with the applications of this plant. The review could be a new starting point for designing further studies with this plant. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.