Dendrobium is one of the most important orchids with high medicinal value. The diverse pharmacological activities of Dendrobium are attributed to its rich content of secondary metabolites. Due to the high variety and content of sesquiterpenoids in Dendrobium, more studies on their pharmacological activities have been reported. More than 100 sesquiterpenoids have been isolated from the roots and stems of Dendrobium, and these compounds have been shown to play important roles in a variety of diseases. However, there is a lack of systematic summarization of the chemical structures and pharmacological activities of sesquiterpenoids in Dendrobium Sw. Here, we reviewed the chemical structures of the sesquiterpenoids in Dendrobium plants, classified them according to the skeleton types, and summarized their pharmacological activities and mechanisms of action, with a view to laying a foundation for future studies on their pharmacological activity mechanisms and rational clinical applications.