Colorectal cancers are a significant cause of mortality in Western societies. The progression of the disease from normal epithelium to the acquisition of the malignant phenotype is accompanied by several biochemical and genetic alterations. Compelling experimental and epidemiologic evidences indicate that diet and nutrition are key factors in modulating colon cancer onset and progression. Therefore, identifying dietary constituents with antitumor activity and investigating their mechanisms of action may lead to significant advances in the prevention of these neoplasms. Moreover, it seems that the potential protection against colorectal cancers of some nutritional factors could be associated with modifications in cellular proliferation and growth. The naturally occurring polyamines, spermine, spermidine, and putrescine, play a key role in hyperproliferation and cell migration and are involved in almost all steps of colorectal tumorigenesis. Mucosal polyamine levels, as a measurement of dysregulated hyperproliferation, have been demonstrated to be significantly associated with cancer risk and have been considered even a specific marker for neoplastic proliferation. Consequently, polyamine metabolism can be considered an attractive target for cancer chemoprevention and chemotherapy. This review summarizes the findings on the possible mechanisms of action of some nutritional components such as flavonoids, polyphenols, and probiotics in colorectal cancers, focusing attention on polyamine metabolism as a possible target. Acquiring more data on this aspect could represent an innovative and interesting approach for new therapeutic and chemopreventive strategies in the management of patients with colorectal neoplasms.