Abstract Berberine is a bioactive compound found in the rhizomes, stems, and fruits of plants belonging to the Berberidaceae, Ranunculaceae, Menispermaceae, Papaveraceae, and Rutaceae families. Although berberine is widely distributed throughout all parts of plants, the bark and root contain significantly higher concentrations of berberine compared with other plant parts. Berberine possesses various pharmacological properties, including antitumor, antibiotic, analgesic, antihyperlipidemic, and anti-inflammatory effects. The bioactive components of berberine are considered promising for the prevention and treatment of various diseases. Berberine has been shown to exert beneficial effects in the management of obesity, diabetes mellitus, cardiovascular and gastrointestinal diseases, cancer, and viral infections. It enhances insulin sensitivity, inhibits gluconeogenesis in the liver, and regulates gut microbiota. While some side effects associated with berberine use have been reported, its overall use is generally regarded as safe, with potential beneficial effects in the treatment of specific diseases. However, it is not appropriate to generalize its beneficial effects in disease prevention. This review highlights the chemical properties, dietary sources, absorption mechanisms, metabolism, biosynthesis, and the promising health benefits of berberine. Current evidence and discussions are examined, and several suggestions for future research are proposed.