The occurrence of colorectal cancer (CRC), which is considered the most prevalent type of cancer globally, is majorly affected by the gut microbiome. The initiation, progression, and reaction of CRC to various systemic treatments are all influenced by the microbiome. Valuable information for CRC screening, early detection, and therapeutic treatment outcomes prediction is obtained by the composition of bacterial species and the contribution of diet to the microbiome. Food components, including proteins, fats, and fibers, stimulate the metabolism of bacteria, which helps with digestion and produces by-products that are extremely important to the host’s function. On the other side, when this equilibrium is upset, the gut microorganisms produce hazardous compounds that have cytotoxic and genotoxic effects. Furthermore, by promoting microbial variety and nourishing the preexisting microbiota, meals high in probiotics and prebiotics can improve the diversity of the microbiome. One of the most promising novel approaches in medicine to enhance personal well-being is microbiome regulation. To ascertain the effectiveness of systemic therapy for CRC, reduce side effects, and raise survival rates, more investigation into the gut microbiome in oncology and in the care of CRC patients is therefore necessary.