Cancer remains a leading cause of mortality globally, necessitating ongoing research and development of innovative therapeutic strategies. Natural products from plants, herbs, and marine species have shown great promise as anti-cancer therapies due to their bioactive components that alter cellular pathways, particularly apoptosis. This review explores the mechanism by which natural chemicals trigger the apoptosis of cancerous cells, which is crucial for eliminating them and halting tumor growth. These can affect the mitochondrial process by controlling the Bcl-2 protein family, increasing cytochrome c release, and activating caspases. They also activate death receptors like Fas and TRAIL to enhance the extrinsic apoptotic pathway. We focus on the main signaling channels involved, such as the endoplasmic reticulum (ER) stress-mediated apoptosis, extrinsic death receptor, and intrinsic mitochondrial pathways. The review explores the role of natural substances such as polyphenols, terpenoids, alkaloids, and flavonoids in promoting apoptotic cell death and increasing cancer cell susceptibility, potentially aiding in cancer treatments and the potential of combining natural products with traditional chemotherapeutic medicines to combat medication resistance and enhance therapeutic efficacy. Understanding cancer development involves inhibiting cell proliferation, regulating it, targeting apoptosis pathways, and using plant and marine extracts as apoptotic inducers.