The root of Asian ginseng (Panax ginseng C.A. Meyer) has been used for centuries in Oriental medicine to improve general well-being and to relieve various medical conditions. It is commonly understood that ginsenosides are responsible for the pharmacological activities of ginseng. Compared to the root of ginseng, studies on the berry are considerably limited. In this study, we evaluated the effects of polysaccharides from Asian ginseng berries on plasma lipid levels, chemically-induced enteric inflammation and neoplasm, and cancer chemoprevention in different experimental models. We tested two polysaccharide preparations: regular ginseng berry polysaccharide extract (GBPE) and ginseng berry polysaccharide portion (GBPP, removed MV [Formula: see text]). We first observed that both oral GBPE and oral GBPP significantly reduced plasma cholesterol and triglycerides levels in a dose-related manner in ob/ob mice, without obvious body weight changes. Then, in AOM/DSS-induced acute colitis mice, GBPE and GBPP significantly ameliorated the increased gut disease activity index and inhibited the reduction of the colon length. Further, the berry polysaccharides significantly suppressed chemically-induced pro-inflammatory cytokine levels. This is consistent with the observation that GBPE and GBPP attenuated tumorigenesis in mice by significantly and dose-dependently reducing tumor load. Finally, in vitro HCT-116 and HT-29 human colon cancer cells were used. While these berry preparations had better antiproliferation effects on the HCT-116 than the HT-29 cells, the GBPE had significantly stronger inhibitory effects than GBPP. The observed in vitro GBPE's effect could contribute to the actions of its small-molecule non-polysaccharide compounds due to their direct antiproliferative activities. Results obtained from the present study suggest that ginseng berry polysaccharides may have a therapeutic role in the management of high lipid levels, enteric inflammation, and colon malignancies.