In this study, microwave assisted puffing technology was developed to increase the extraction efficiency of polysaccharides from D. devonianum. Fresh stems of Dendrobium devonianum were processed using microwave puffing technology and the processing conditions were explored and optimized to increase the extraction yield of polysaccharides. The effects of sample length (SL), initial moisture content (IMC), microwave power (MP), and processing time (PT) on quality attributes of the products, in terms of expansion ratio and sensory evaluation, were analyzed using response surface methodology. The optimal SL, IMC, MP, and PT were 3.5 cm, 22%, 702 W, and 31 s, respectively, which resulted in optimal expansion ratio and sensory score of 326.1% and 8.63, respectively. Furthermore, the extraction yield of polysaccharides from the microwave-puffed products was increased by 18.9% compared with that from nonpuffed samples. Antioxidant and anti-hyperglycemic activities of polysaccharides from puffed and nonpuffed D. devonianum were also evaluated and compared. Practical applications: We developed a novel microwave assisted puffing technology to increase the extraction efficiency of polysaccharides from D. devonianum. Polysaccharides, the major active components of Dendrobium species, exhibit the potential as an inhibitor, including immunomodulator, antioxidant, anti-tumor and anti-hyperglycemic agent.