Mesona chinensis Benth has been consumed as a functional food for many years. It is widely believed that storage times affect its health benefits. In this study, Mesona chinensis Benth polysaccharides with two different storage times (fresh and storage for 1 year) were prepared, namely, FMP and AMP. The physicochemical properties and bioactivity were comparatively assessed. Results indicated that FMP was mainly composed of galacturonic acid, galactose, and glucose with a molecular weight of 44.39 kDa. AMP was composed of galacturonic acid, galactose, and fructose with a molecular weight of 64.34 kDa. However, the principal structural characteristics of polysaccharides remained stable. Furthermore, assays of antioxidant activity showed that Mesona chinensis Benth polysaccharide had an antioxidant effect against DPPH radical, ABTS radical cation, among which FMP was stronger. Additionally, flow cytometry indicated that the apoptosis rate of FMP and AMP on HepG2 tumor cells was 22.50 ± 1.25% and 15.49 ± 1.30%, respectively. In general, antioxidant and antitumor activities of Mesona chinensis Benth polysaccharides were decreased as the storage for 1 year. The change of physicochemical properties was responsible for the enhanced bioactivities. These results explained how polysaccharides contributed to the decreased health benefits of Mesona chinensis Benth during storage.