Chalcones are the basic chemical structural predecessors of flavonoids and isoflavonoids, frequently available in many innately arising compounds. Chalcones and their counter parts have drawn the attention of many researchers because of their extensive pharmacological activities with therapeutic potential against various clinical conditions, especially for anticancer activity. The chalcone derivatives potentially suppress the growth of tumors through multiple mechanisms, encompassing interfering cell division, control of cell degradation, triggering cell suicide, and regulating the immune response towards cancer cells and inflammatory mediators. The benefits of chalcones are consistent that researchers develop chalcone derivatives asnovel cancer therapeutic agents. Combination therapy (chalcone derivatives with other chemotherapeutic agents) is even more effective in curing colon cancer. The preclinical findings of treating cancer cells with chalone derivatives were encouraging suggesting their potential use clinically in cancer patients. However, further investigations and a complete study of the degree of toxicity associated with chalcone derivatives are required. The current review summarizes the pharmacological and immunological properties of chalcones and their anticancer activities with their possible mechanisms of action in colon cancer.