Garlic possesses a broad spectrum of medicinal properties, such as anti-cancer, antioxidant, anti-diabetic effects, and protective effects on the heart, nervous system, and liver. Diallyl disulfide (DADS), an oil-soluble organic sulfur-containing compound in garlic, has garnered attention in recent years for its demonstrated anti-cancer efficacy in various cancer types such as leukemia, breast cancer, hepatocellular carcinoma, stomach cancer, and prostate cancer. The anticancer properties of DADS are attributed to its ability to suppress cancer cell proliferation, impede invasion and metastasis, as well as induce apoptosis, promote differentiation, and facilitate cell cycle arrest. Although many literatures have reviewed the pharmacokinetics, molecular mechanisms of anti-cancer effects and some clinical trials of DADS, the specific mechanisms and clinical-translational therapeutic potentials have not been elucidated. This comprehensive review focuses on delineating the molecular mechanisms underlying the anticancer effects of DADS, with a particular emphasis on its potential utility as a therapeutic intervention in the clinical management of cancer, and analyzes the challenges and coping strategies faced in the application of DADS as an anti-cancer drug, pointing out the directions for scientific research.