Development and identification of molecular compounds capable of killing or inhibiting transformed cells promoting carcinogenesis without inducing toxic effects to the normal cells are of utmost significance. A systematic review was conducted in screening for important literature was extensively performed by searching the Web of Science, Ovid, BMC Springer, Elsevier, Embase, and MEDLINE databases for optimum selectivity. Google Scholar was also used to supplement information. Pharmacotherapeutic biomolecules active against colon cancer carcinogenesis in Musa acuminata and Musa balbisiana (bananas), Punica granatum L (pomegranate), Glycine max (Soybean), Brassica oleracea L var. italica Plenck (Broccoli), and Hibiscus rosa-sinesis and Hibiscus sabdariffa (hibiscus) were evaluated. Signaling pathways like phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), protein kinase B (AKT), and nuclear factor-kappa B (NFκB) correlate the mediation of COX-2 expression. Increased levels of COX-2 are correlated with the occurrence and progression of colon cancer. Natural antioxidants in herbal plants including polyphenols and carotenoids inhibit the oxidation of lipids, proteins, and nucleic acids and thereby preventing the initiation of oxidizing chain reactions. These bioactive compounds should be considered an important dietary supplement.