Recent advancements in microbiome research have underscored the critical role of gut microbiota in human health and disease. Among the emerging concepts in this field, postbiotics have gained significant attention for their potential therapeutic benefits, particularly in colorectal cancer (CRC). Postbiotics, which encompass various bioactive compounds produced by beneficial gut microbes, exert multifaceted effects on host physiology, immune response, and gut barrier integrity. This chapter explores the intricate interplay between postbiotics and CRC, encompassing their mechanisms of action, preclinical and clinical evidence, and therapeutic implications. Additionally, it discusses the potential of postbiotics as novel preventive and therapeutic strategies against CRC, highlighting their promise in modulating the gut microenvironment and influencing tumor development. By elucidating the complex interactions between postbiotics and CRC, this chapter aims to provide insights into future research directions and clinical applications in harnessing the therapeutic potential of postbiotics for colorectal cancer management.