Inflammatory bowel disease (IBD) is comprised of ulcerative colitis (UC) and Crohn's disease (CD) that was recognized by the inflammation in the colon. There are no proper medications are available to control the IBD in patients. NASIDs such as Aspirin, diclofenac, and ibuprofen are widely used to control the inflammation. On the other hand, the untreated prolonged inflammation leads to the development of cancer in the colon termed as colitis-associated cancer or inflammation-driven colon cancer. Oxidative stress and inflammation play key roles in the pathogenesis of colitis-associated cancer. Single dose of azozymethane (AOM) and three cycles of 2% dextran sodium sulfate (DSS) induces colitis-associated cancer (CAC) in mouse. Hence, many natural products were tested in the preclinical model of colitis-associated cancer. Each of these natural agents modulate important signaling pathway to control the colitis-associated cancer (CAC). In this review, the authors tabulated all the natural agents that culminate the colitis-associated cancer in the preclinical models.