Background: Ginseng is a commonly used herbal medicine in treating various medical conditions. Chronic gut inflammation is a recognized factor for the development of colorectal cancer (CRC). In thisproject, Asian ginseng berry polysaccharide preparations were used to assess their effects on CRC andrelated immune regulation mechanisms. Methods: Ginseng berry polysaccharide extract (GBPE) and purified ginseng berry polysaccharideportion (GBPP) were used to evaluate their activities on human HCT-116 and HT-29 CRC cell proliferation. Interleukin-8 secretion analysis was performed on HT-29 cells. Naive CD4 cell isolation and T-helper celldifferentiation were performed and determined using flow cytometry for Th1 and Treg in addition to cellcycle and apoptotic investigation. Results: GBPE and GBPP significantly inhibited interleukin-8 secretion and cancer cell proliferation,inhibited CD4þIFN-gþ cell (Th1) differentiation, and decreased CD4þFoxP3þ cell (Treg) differentiation. Compared to the GBPE, GBPP showed more potent antiinflammatory activities on the malignant cells. This is consistent with the observation that GBPP can also inhibit Th1-cell differentiation better, suggestingthat it has an important role in antiinflammation, whereas Treg cells hinder the body’s immuneresponse against malignancies. Supported by cell cycle and apoptosis data, GBPE and GBPP, at variousdegrees, remarkably enhanced the anticancer activities of 5-fluorouracil. Conclusion: Data from this project suggested that Asian ginseng berry potentially has clinical utility inmanaging enteric inflammation and suppressing CRC through immunomodulation mechanisms.