Colon cancer poses a significant global health challenge, demanding innovative therapeutic approaches. Chalcones, a versatile group of compounds with diverse pharmacological properties, have emerged as promising candidates in the fight against colon cancer. Their capacity to modulate key signaling pathways during the development and progression of colon cancer positions them as invaluable targeted therapeutics. Nevertheless, it is crucial to recognize that, although chalcones exhibit potential, further pre-clinical investigations are necessary to substantiate their effectiveness and safety. The path to successful colon cancer treatment is multifaceted, involving considerations such as optimizing the sequence of therapeutic agents, understanding resistance mechanisms, and exploring combination therapies that integrate chalcones. Additionally, the integration of drug delivery systems based on nanoparticles offers a new approach to enhance the efficacy of chalcones in colon cancer treatment.