Abstract Colorectal cancer (CRC) therapy is limited by resistance and toxicity. Traditional Chinese medicine (TCM) alkaloids, with multi‐target potential, offer a promising complementary strategy. This review synthesises their anti‐CRC mechanisms and therapeutic potential. A systematic literature review was conducted according to established guidelines. Scientific databases including Web of Science were searched using specific keywords such as ‘alkaloid’, ‘colorectal cancer’ and ‘traditional Chinese medicine’. The botanical sources, chemical classification, molecular targets and multi‐level anti‐tumour mechanisms of TCM alkaloids were analysed. Pharmacokinetic challenges and delivery strategies of key compounds were also evaluated, integrating evidence from cellular, animal and emerging clinical studies. Inhibition of CRC progression was achieved through multiple validated mechanisms. Cell cycle arrest and apoptosis were induced, while metastasis and angiogenesis were suppressed. The tumour microenvironment and gut microbiota were effectively modulated. For key alkaloids, specific molecular targets and interaction modes were identified. Furthermore, novel delivery systems were developed to overcome pharmacokinetic limitations. Synergistic effects with conventional chemotherapy were also demonstrated. The multi‐target actions of TCM alkaloids position them as ideal candidates for integrative CRC therapy. This review provides a foundation for their future development as novel agents or adjuvants, warranting further translational and clinical studies to validate their efficacy.
Cong et al. (2026) studied this question.