Mangiferin (MGF) is a phenolic compound, which is a major source of MGF is the mango tree. MGF possesses some antioxidant, anti‐inflammatory, and cytoprotective properties, enabling it to play its role against various diseases such as diabetes, obesity, lung injuries, and cancer. The word “Cancer” depicts an uncontrolled and abnormal growth of cells. This review paper reveals MGF's therapeutic, curative and protective potential impact against lung, liver, ovarian, prostate, breast, stomach, and oral cancers. MGF is used in various types of research in the form of powder, liquid extract, intramuscular, intravenous, nanoparticles coated with gold, in the form of a solution, or in combination with other drugs to evaluate synergistic effects. Many studies showed that MGF is safe to use but has less bioavailability in the body and 0.111 mg/mL solubility in water. However, certain studies indicated that its bioavailability and retention time increased when taken in the form of nanoparticles and in combination with other drugs. MGF also increases the sensitivity of other drugs (i.e., cisplatin) resistant to tumors. MGF has different mechanisms of action for different cancers. It mainly targets enzymes, interleukins, tumor growth factors, signaling pathways, apoptotic proteins, and genes to inhibit the growth of tumors, volume, angiogenesis, cellular functionality, further progression, and movement to other areas of the body. Moreover, MGF increases apoptosis and body weight with no or fewer side effects on normal cells. MGF unveiled a novel gate toward the treatment of cancer. Further research and human trials are needed in this regard.