Over the last two decades, molecular biology advances have revealed the gut microbiota's active and crucial role in colorectal cancer (CRC) pathogenesis and its dysregulation during tumorigenesis. This understanding has underscored the urgency of exploring novel therapeutic approaches to address the challenges posed by CRC. Among these approaches, nanosynergistic therapies, with their potential to modulate the gut microbiota, increase drug bioavailability and stability, and reduce side effects, have emerged as a promising avenue. Furthermore, the efficacy of nanotechnology-based approaches can be enhanced by combining them with different therapeutic methods, including chemotherapy, radiotherapy, immunotherapy, photothermal therapy, and sonodynamic therapy. Herein, recent progress in nano synergistic therapy has been reviewed, focusing on the synergy between gut microbiota and nanotechnology in CRC treatment. Additionally, the diverse applications of nanoparticles have been analyzed to provide innovative ideas and effective solutions for developing highly effective CRC treatment strategies.