Ultrasonic-enzymatic extraction of Polygonatum odoratum polysaccharide was used in this study. The extracted polysaccharide was prepared into effervescent tablets with anti-fatigue function. Single factor test and orthogonal test were carried out to determine the best extraction conditions. The results showed that the optimal conditions were ultrasonic time 30 min, ultrasonic temperature 30 ℃, liquid to solid ratio 30∶1, cellulase content 2.2%, and the extraction rate of crude polysaccharides was up to 6.13%. Using the extracted polysaccharide with acesulfame potassium, effervescent and other auxiliary materials, the anti-fatigue effervescent tablets with Polygonatum odoratum polysaccharide were prepared. The optimal formula is 25% Polygonatum odoratum polysaccharide, the ratio of citric acid to sodium bicarbonate is 1.0∶1, and acesulfame potassium is 6%. The experimental results show that the effervescent tablet has a certain anti-fatigue effect, and can significantly reduce the content of serum urea nitrogen in mice.