Datura (Solanaceae), a traditional Chinese medicine, has been used to treat arthralgia, asthma, cough, gastrointestinal cramps, neuropathic migraine, and injuries from falls. More than 432 bioactive constituents were isolated and identified from different species of Datura, including steroids, alkaloids, flavonoids, terpenoids, phenolics, and aliphatics compounds. Pharmacological studies demonstrated that Datura extracts and the compounds showed anti-inflammatory, analgesic, antibacterial, antioxidant, anti-cancer, cell protection, and insect-repellent activities. However, many studies were mainly based on extracts, the bioactive ingredients, and the mechanisms for their folk application; other ingredients have not been well identified, and there is also a gap in research regarding their clinical effects and safety. Thus, more detailed studies on the mechanisms and additional clinical studies on the extract and compounds from Datura are needed to ensure the safety and effectiveness of the plant for further use. In this review, we collate the current information on Datura, including its ethnobotanical uses, phytochemistry, known biological activities, and toxicological properties, to understand their current situation and provide a scientific basis for their further use.