<p>Colorectal cancer (CRC) is a second leading cause of human mortality worldwide. Due to the inconsistent effectiveness of traditional anticancer therapies, there is an increasing need for novel drug-free cancer therapy that enhances the efficacy of current treatments with minimum side effects. CRC is linked to microbiome modifications, a phenomenon termed dysbiosis, which entails the reduction and/or augmentation of certain gut bacteria and their metabolites. Administration of next-generation probiotics (NGP) may serve as an effective and accessible cancer treatment by regulating gut microbiota composition. The review provides a focused analysis of NGPs in CRC, highlighting their preventive and therapeutic roles, modulation of gut microbiota and signaling pathways, and current translational progress. Restoration of intestinal microbiota in cancer patients may promote anti-inflammatory, anticarcinogenic, immunomodulatory, and other physiologically significant pathways that exhibit high selectivity for tumor cells. The potential advantages of NGP include the modulation of intestinal microbial community and functionality, in addition to influencing the host’s inflammatory response. NGPs that help maintain gut balance include <i>Bacteroides fragilis, Akkermansia muciniphila, Propionibacterium freudenreichii</i>, and specific strains of <i>Clostridium</i> spp. This review emphasizes their applicability in CRC prevention, with promising preclinical evidence from animal models. Recent evidence suggests that NGP may provide novel therapeutic approaches for CRC by facilitating physiological processes via the generation of immuno-modulatory metabolites that counteract CRC. Despite the observed positive outcomes in preclinical studies, more research concentrating on targeted strain, safe use, and dosage specificity is necessary to confirm the effectiveness and safety profile of NGP in the treatment of CRC.</p>