In Chinese medicine, the Cucurbitaceae family contains many compounds known as cucurbitacins, which have been categorized into 12 classes ranging from A to T and more than 200 derivatives. Cucurbitacins are a class of highly oxidized tetracyclic triterpenoids with potent anticancer properties. The eight components of cucurbitacins with the strongest anticancer activity are cucurbitacins B, D, E, I, IIa, L-glucoside, Q, and R. Cucurbitacins have also been reported to suppress JAK-STAT 3, mTOR, VEGFR, Wnt/β-catenin, and MAPK signaling pathways, all of which are crucial for the survival and demise of cancer cells. In this paper, we review the progress in research on cucurbitacin-induced apoptosis, autophagy, cytoskeleton disruption, cell cycle arrest, inhibition of cell proliferation, inhibition of invasion and migration, inhibition of angiogenesis, epigenetic alterations, and synergistic anticancer effects in tumor cells. Recent studies have identified cucurbitacins as promising molecules for therapeutic innovation with broad versatility in immune response. Thus, cucurbitacin is a promising class of anticancer agents that can be used alone or in combination with chemotherapy and radiotherapy for the treatment of many types of cancer.Therefore, based on the research reports in the past five years at home and abroad, we further summarize and review the structural characteristics, chemical and biological activities, and studies of cucurbitacins based on the previous studies to provide a reference for further development and utilization of cucurbitacins.