Abstract: In this study, pumpkin skin polysaccharide zinc was prepared from pumpkin skin polysaccharide and zinc. The optimal preparation process of pumpkin skin polysaccharide zinc was optimized by single factor and response surface methodology, and the bioavailability of zinc ion in pumpkin skin polysaccharide zinc was determined by simulated gastrointestinal digestion in vitro. The results showed that the optimum preparation process of pumpkin skin polysaccharide zinc was as follows: The mass ratio of pumpkin skin polysaccharide to zinc was 18:1, the reaction time was 104 min and the reaction pH was 9. Under these conditions, the chelation rate reached the maximum value of 99.37%±0.12%. The content of zinc determined by inductively coupled plasma mass spectrometry was about 23.17±0.05 mg/g. In vitro simulated gastrointestinal digestion experiment showed that polysaccharide zinc was less affected by the acidic environment in the stomach, and the dissolution rate and dialysis rate of zinc ion in polysaccharide zinc were higher than that of inorganic zinc in the intestine. The results showed that pumpkin skin polysaccharide zinc had high bioavailability and good stability, which would provide a basis for developing new polysaccharide zinc supplement and improving the comprehensive utilization of pumpkin resources.