Agaricus blazei Murill polysaccharide (ABMP) has been found to exhibit significant immune regulatory effects, making them a promising candidate for complementary to the pharmacological treatment of colorectal cancer immune-related diseases. As the prevalence of colorectal cancer among younger individuals increases, the possible age-dependent anticancer modulatory effect of ABMP has not been clarified. This study evaluated the age-dependent immunoregulatory efficacy of polysaccharides extraction from A. blazei in colon tumor. Hematoxylin-eosin staining, immunohistochemistry, and vibrational spectroscopic image analysis of subcutaneous tumor tissues after ABMP preventive intervention for 14 weeks were analyzed in depth. In vivo data demonstrated that ABMP could more effectively inhibit the growth of tumor in mice at 8 compared with 12 months old without toxic side effect. Concurrently, Raman imaging spectroscopy analysis showed that ABMP preventive intervention could significantly reduce the lipid content in the tumor microenvironment (TME) of 8-month-old subcutaneous tumor-bearing mice, suggesting that the changes in lipid content in TME are closely related to anticancer activity. These results stress the importance of considering age as a factor in polysaccharide adjuvant anticancer therapy. This work highlights for the first time that age is a key determinant in the ABMP preventive effectiveness by affecting lipid levels in the TME of tumor-bearing mice, thereby exerting anticancer activity.