Polygonatum odoratum is rich in polysaccharides, which are key bioactive components with significant pharmacological value. To optimize their extraction and utilization, it is crucial to identify the growth stage during which polysaccharides are most abundant. In this study, we investigated the seasonal dynamics of polysaccharide accumulation and protein expression in Polygonatum odoratum rhizomes via wide-targeted metabolomics and proteomics. The total polysaccharide content peaked in spring (13.3%), with the second highest level occurring in winter. A total of 610 differentially expressed proteins (DEPs) were identified, with the highest number of DEPs upregulated in spring. Weighted gene coexpression network analysis (WGCNA) revealed a module highly correlated with polysaccharide accumulation and enriched in pathways such as “starch and sucrose metabolism.” Key enzymes, including invertase (INV) and hexokinase (E2.7.1.4), were significantly upregulated in spring and positively correlated with polysaccharide biosynthesis. These results provide valuable insights into the optimal harvest time (spring) for Polygonatum odoratum and identify potential molecular targets for breeding high-polysaccharide varieties.