ABSTRACTThe most prevalent and bioactive cucurbitacin is Cucurbitacin B (CuB, C32H46O8), which is a tetracyclic triterpene chiefly present in the Cucurbitaceae family. CuB has a wide spectrum of pharmacological properties namely antioxidant, anticancer, hepatoprotective, anti‐inflammatory, antiviral, hypoglycaemic, insecticidal, and neuroprotective properties, owing to its ability to regulate several signaling pathways, including the Janus kinase/signal transducer and activator of transcription‐3 (JAK/STAT3), AMP‐activated protein kinase (AMPK), nuclear factor (NF)‐κB, nuclear factor erythroid 2‐related factor‐2/antioxidant responsive element (Nrf2/ARE), phosphoinositide 3‐kinase (PI3K)/Akt, mitogen‐activated protein kinase (MAPK), Hippo‐Yes‐associated protein (YAP), focal adhesion kinase (FAK), cancerous inhibitor of protein phosphatase‐2A/protein phosphatase‐2A (CIP2A/PP2A), Wnt and Notch pathways. The present review highlights the medicinal attributes of Cucurbitacin B (CuB) with special emphasis on their signaling pathways to provide key evidence of its therapeutic utility in the near future.