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Colon cancer is the second most invasive cancer and fourth most common malignant neoplasm worldwide. Targeted oral colonic drug delivery systems have attracted considerable attention in the treatment of colon cancer due to their superior properties. However, the delivery of drugs safely and effectively to the target site of the colon tumor is a hindrance due to the complexity of the gastrointestinal structure. Herein, to achieve an effective delivery system specifically targeting the colon, we have taken concern by using natural polymer such as pullulan, signifying its flexibility and relevance in biomaterials science to design antineoplastic approaches. Here, we summarize the physicochemical properties, different pullulan derivatives and their biomedical application, several colon cancer‐related treatment, and pullulan and its derivatives‐based delivery systems towards colonic tissue.