Dioscorea spp. belongs to the Dioscoreaceae family, known as “yams”, and contains approximately 600 species with a wide distribution. It is a major food source for millions of people in tropical and subtropical regions. Dioscorea has great medicinal and therapeutic capabilities and is a potential source of bioactive substances for the prevention and treatment of many diseases. In recent years, increasing attention has been paid to the phytochemicals of Dioscorea, such as steroidal saponins, polyphenols, allantoin, and, in particular, polysaccharides and diosgenin. These bioactive compounds possess anti-inflammatory activity and are protective against a variety of inflammatory diseases, such as enteritis, arthritis, dermatitis, acute pancreatitis, and neuroinflammation. In addition, they play an important role in the prevention and treatment of metabolic diseases, including obesity, dyslipidemia, diabetes, and non-alcoholic fatty liver disease. Their mechanisms of action are related to the modulation of a number of key signaling pathways and molecular targets. This review mainly summarizes recent studies on the bioactive compounds of Dioscorea and its treatment of inflammatory and metabolic diseases, and highlights the underlying molecular mechanisms. In conclusion, Dioscorea is a promising source of bioactive components and has the potential to develop novel natural bioactive compounds for the prevention and treatment of inflammatory and metabolic diseases.