Oral colon-specific delivery system (OCDS) is a targeted approach that aims to directly deliver bioactive compounds directly to the colon following oral administration, thereby enhancing the colonic release of bioactive substances and minimizing adverse reactions. The effectiveness of bioactive substances in the colon hinges on the degree of release, which are affected by various factors including pH, mucosal barrier, delivery time and so on. Therefore, this review provides a comprehensive overview of the key factors affecting oral colon-specific release of bioactive components firstly. Considering the oral safety, this review then mainly focuses on the types of carriers with edible OCDS and preparation strategies for OCDS. Finally, several preparation strategies for loading typical natural bioactive ingredients into oral safe OCDS are reviewed, along with future development prospects.