Cancer is a significant contributor to premature mortality on a global scale. Its high prevalence and resistance to drugs currently used in the clinical practice have prompted the search for new treatment alternatives. Secondary metabolites from plants are considered to be a primary source of novel anticancer agents, and studies suggest that modulation of circular RNAs (circRNAs) is involved in some of their mechanisms of action, impairing cancer cell proliferation, inducing cell death pathways, and improving chemotherapy resistance. circRNAs are a class of non-coding RNAs (ncRNAs) that have provided new insights into several diseases, including cancer. In terms of function, circRNAs exert a significant influence on gene expression, either directly or indirectly. The aim of this chapter is to provide an overview of the existing research on the effect of alkaloids, flavonoids, and terpenes as products from the secondary metabolism of plants in the modulation of circRNAs in tumor cells. The alkaloids berberine, matrine, oxymatrine, and nitidine chloride, the flavonoids baicalein, genistein, icariin, icaritin, and luteolin, and the terpenes curcumol, tanshinone I, triptolide, astragaloside IV, ginsenoside Rg3, and ganoderic acid have been identified as natural products that target circRNAs. Taken together, these findings suggest that natural products targeting circRNAs act through a circRNA-miRNA-protein axis. This is because circRNAs primarily act as miRNA sponges, regulating oncogenes, transcription factors, and enzymes. It can be concluded that research into the modulation of circRNA expression will help to elucidate the mechanisms of action of compounds considered as potential anti-cancer drugs, thereby guiding the development of new treatment alternatives and facilitating the understanding of the modulation of some of the many dysregulated biological pathways in tumors.