Abstract: Dendrobium officinale Kimura et Migo (D. officinale) has been used as a valuable traditional Chinese medicine for more than 2 000 years in China. Modern research has confirmed a wide range of pharmacological activities, such as regulating blood sugar, improving gastrointestinal inflammation, and regulating immunity. Polysaccharides are the main active ingredients of D. officinale. With the intensive studies of the pharmacological activities of D. officinale, evidence for the pharmacological effects and potential mechanisms of D. officinale polysaccharides has increased dramatically. In this review, we summarized the latest progress in the pharmacological and mechanical studies of D. officinale polysaccharides, and based on the pharmacological efficacy and oral absorption and utilization characteristics of D. officinale polysaccharides, it is proposed that regulating the gut microbiota may be one of the key mechanisms for D. officinale to exert its beneficial effects. Research on the mechanism of D. officinale polysaccharides puts forward new research directions and prospects.