Background Coccinia grandis (L.) Voigt, commonly known as Ivy gourd, is a plant of the Cucurbitaceae family that has been used in traditional medicinal systems for centuries. Its most common traditional use is managing diabetes mellitus which has been scientifically proven along with other pharmacological activities. Objective This review aims to thoroughly explore the scientific evidence of various pharmacological activities of C. grandis and its therapeutic applications. Method A thorough search of the literature was carried out to identify relevant research on C. grandis. With the combination of the plants’ scientific names, different keywords, such as “Coccinia grandis” “Coccinia indica” “traditional medicine” “ethnobotany” “ethnomedicine” “phytochemistry” “bioactive compounds” “pharmacology” “health benefit” “side effect” “toxicity” and “clinical trial”, have been used for search using Boolean operators. Retrieved articles were strictly screened to maintain inclusion criteria. One hundred and sixty-nine papers were eventually chosen for this review after a thorough examination of the retrieved articles that matched the inclusion and exclusion criteria. Results C. grandis was found to have a number of compounds that are biologically active and exhibit anti-diabetic, anti-dyslipidemic, anti-obesity, anti-oxidant, anti-inflammation, anti-cancer, analgesic, anti-oxidant, antinociceptive, antipyretic, anthelmintic, analgesic, spasmolytic, wound-healing, anti-ulcerogenic, anti-convulsant, hepatoprotective and immunomodulatory activities without obvious side effects. Nanoparticles produced from the plant and different extracts of the plant show excellent anti-microbial activity. Conclusion The scientific evidence encourages exploring more in-depth experimental studies regarding the pharmacological activities to develop C. grandis as a novel therapeutic agent.