<p>Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, and new treatment options are urgently needed. Drug repositioning has gained attention as a strategy to identify new therapeutic applications for CRC. This approach can expedite drug development and reduce costs by leveraging drugs already undergoing safety testing. Computational and experimental methods are used to identify potential candidates for drug repositioning in CRC. However, challenges such as a lack of comprehensive knowledge regarding the molecular mechanisms underlying the disease and resolving intellectual property and regulatory issues must be overcome. Drug repositioning has the potential to revolutionize CRC treatment by identifying new drugs for gastrointestinal tumors. For example, metformin, a biguanide antidiabetic drug, is effective for CRC by inhibiting the PI3K-Akt-mTOR pathway. COX-2 inhibitors, which block cyclooxygenase-2 to reduce inflammation and cancer progression, may also be examples of drug repositioning for CRC. Several approaches have been employed to identify potential candidates for drug repositioning in colorectal cancer, including computational methods such as data mining and network analysis and experimental techniques such as high-throughput screening and in vitro assays. Despite its potential benefits, drug repositioning in colorectal cancer faces several challenges, including the lack of comprehensive knowledge regarding the disease’s molecular mechanisms. Further research is needed to overcome these challenges and identify specific drug targets for CRC treatment. With continued efforts and advancements in this field, drug repositioning has the potential to revolutionize colorectal cancer treatment. This review provides an overview of drug repositioning in the context of colorectal cancer, highlighting its advantages, challenges, and potential future directions.</p>