<p>Colon cancer (CC) is a leading cause of cancer-related mortality worldwide, and its poor prognostic outcome can be attributed to factors such as late diagnosis, tumor heterogeneity, and the failure of conventional chemotherapeutic therapies. Biomimetic nanomaterials that can mimic biological behaviors have recently generated transformative drug carriers with higher biocompatibility, evasion of the immune system, and tumor-seeking capabilities. In this review, recent progresses in biomimetic systems are summarized, such as cell membrane-coated nanoparticles, exosome-based carriers, and ligand-modified nanostructures, with a particular focus on their design paradigm and drug delivery mechanisms and the therapeutic potentiality in CC. Although preclinical investigations reveal potential response, translational barriers to clinical application remain considerable including but not limited to scalability in nanomaterial manufacturing, batch variability in produced materials, and regulatory challenges under FD/EMA regulation. Possible solutions involve cost-effective and scalable macrofluidic and automated bioreactor technologies, comprehensive protocols of exosome isolation and nanoparticle characterization, and systemic harmonization with regulatory frameworks for safety and quality at a stage earlier than the end of the process. Future directions towards combining biomimetic nanocarriers with gene-editing tools, immunotherapies, and phytochemical-based agents for synergistic effects, and the development of novel theranostic systems integrating diagnosis and treatment will be pursued. Overcoming these translational hurdles and interdisciplinary collaborations are critical for biomimetic nanomaterials to fulfil their huge potential to move colon cancer therapy closer to a safer, more effective and clinically practicable reality.</p>