Natural compounds and their derivatives have been identified as valuable sources of therapeutic ingredients for cancer treatment. The naturally occurring phytochemical palmatine (isoquinoline alkaloid) is extracted from plant parts (rhizomes, roots, stems, stem barks, and others) and has protective effects including antioxidant, anti‐inflammatory, and anticancer. This study aims to summarize the anticancer potential of palmatine and its derivatives in the treatment of numerous types of cancer with molecular mechanisms. We also include the pharmacokinetic features, botanical origin, and toxicological characteristics of palmatine and its derivatives. For this, data have been collected from plausible different electronic databases, including PubMed, Google Scholar, PubChem, Science Direct, Web of Science, Scopus, Springer Link, and Wiley Online. The findings demonstrate that palmatine and its derivatives have a protective anticancer effect against a variety of cancers, including breast, colorectal, gastric, ovarian, prostate, pancreatic, skin, hepatocellular cancer, and mammary gland tumors. They provoke their anticancer properties against various cancer cell lines via modifying molecular mechanisms like induction of oxidative stress, cytotoxicity, apoptosis, inhibition of cell invasion and migration, arresting the cell cycle at the S phase, antiproliferative, and antiangiogenic effects. It is suggested that palmatine and its derivatives may be a good option in the development of novel drugs for cancer therapy in the future.