Multidrug resistance is one of the major obstacles to successful cancer chemotherapy, which causes cancer to remain one of the leading causes of death worldwide. Therefore, the use of natural products for cancer prevention and therapy has been continuously investigated and developed for decades. Alkaloids are one of the important compounds derived from natural products that have been extensively studied for their potential use as cancer chemopreventive and chemotherapeutic drugs in both in vitro and animal studies. This short review intends to present the molecular mechanisms of action of alkaloids on stimulation and inhibition some signaling molecules involved in cell proliferation, differentiation, angiogenesis, metastasis and apoptosis pathways of cancer cells. The understanding of the molecular mechanisms of alkaloids against cancer will provide clues towards a diagnostic, prevention and therapeutic applications. Based on the information provided in this article, alkaloids show remarkable potential as anticancer agents. However, more research and clinical trials are crucial before applying any of these alkaloids as new medicine to treat cancer patients.