This review delineates the key metabolic enzymes (HK2, GLUTs, PKM2, LDH, PDH, G6PD) modulated in CRC and provides an overview of the effects of 39 natural compounds derived from three species on metabolic enzymes, related proteins, oncogenes, and the interconnected pathways specific to colorectal carcinogenesis. The gene discussed is PKM; the disease is colorectal carcinoma.