Background: Bondarzewia dickinsii (BD) is a newly discovered edible mushroom with rich nutritional components. This study presents a thorough analysis of the components of BD, examining its inhibitory effects and the underlying mechanisms by which BD influences colitis-associated cancer (CAC). Methods: AOM/DSS-induced CAC mice (male C57BL/6) were used, and a histopathological analysis, intestinal microbiota assessment, and metabolomics profiling were carried out, as well as an evaluation of relevant proteins and factors, to investigate the CAC-inhibitory effects of BD. Results: BD is rich in nutritional components, including a total sugar content of 37.29% and total protein content of 24.9%. BD significantly diminished colon inflammation, as well as the size and quantity of tumors. In addition, BD modified the diversity of intestinal microbiota and changed the levels of 19 serum metabolites, including arachidonic acid. BD significantly reduced prostaglandin E2 (PGE2) and cyclooxygenase-2 (COX-2) in colon tissue. Furthermore, it was found to inhibit the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/COX-2 signaling pathway. Conclusions: In general, BD inhibited the onset and progression of CAC by modulating the composition of intestinal microbiota and metabolite levels, suppressing the PI3K/AKT/COX-2 pathway, and decreasing PGE2 expression. This study provides a significant reference for the development of BD as a dietary supplement and pharmaceutical agent in the treatment of CAC.