Numerous research studies have linked colorectal cancer (CRC), the third-highest-recurring cancer in the world, to microbiota in the gut, a complex system of bacterial communities essential to metabolic regulation, immune system control management, and the maintenance of intestinal homeostasis. A deficiency in the microbiota that is present in the gut has been strongly connected to the development of CRC through chronic swelling, inflammation, immune resistance, and metabolic dysregulation. Because of their stability and safety relative to live probiotics, postbiotics—defined as nonviable microbial cells, their components, or metabolic by-products—have become attractive therapeutic agents in CRC treatment. These bioactive substances change important molecular pathways to have anticancer properties. Recently discovered short-chain fatty acids (SCFAs) such as butyrate block the histone deacetylases (HDACs), which leads to activated tumor suppressor genes as well as the death of CRC cells. In addition, postbiotics can interact with G-protein-coupled receptors (GPCRs), for example, GPR41 and GPR43, reducing inflammation as well as increasing the immune response. They can also raise the health of your gut through the growth of beneficial bacteria and prevent pathogenic organisms such as Fusobacterium nucleatum and necrophorum both known as contributors to CRC. Through stimulating tight junction proteins, they also improve the intestinal barrier and prevent the transmission of harmful bacteria and contaminants that could cause carcinogenesis. This chapter explores the cellular mechanisms underlying the role of postbiotics in the management of colorectal cancer. It also outlines their ability to be a revolutionary therapy for the prevention and treatment of cancer, especially in those suffering from dysbiosis-related CRC.