Jatropha gossypifolia L. (Euphorbiaceae), commonly known as Bellyache Bush or Red Physic Nut, is an important medicinal shrub widely distributed throughout tropical and subtropical regions of the world. The species has been extensively employed in traditional systems of medicine, including Ayurveda, folk medicine, and ethnoveterinary practices, for the management of skin disorders, inflammation, wounds, gastrointestinal ailments, fever, rheumatism, hypertension, and infectious diseases. Different plant parts, including leaves, roots, bark, latex, seeds, and seed oil, contain diverse classes of bioactive compounds such as diterpenoids, flavonoids, lignans, coumarins, alkaloids, steroids, phenolic compounds, and triterpenoids that contribute to its broad spectrum of biological activities. Pharmacological investigations have demonstrated significant antimicrobial, antioxidant, anti-inflammatory, analgesic, wound-healing, hepatoprotective, antidiabetic, anticancer, antiviral, insecticidal, and antihypertensive properties. However, the presence of toxic constituents, particularly phorbol esters and toxalbumins, necessitates careful evaluation of safety before therapeutic application. Recent advances in phytochemical profiling, molecular pharmacology, biotechnology, and nanotechnology have further expanded the pharmaceutical prospects of this medicinal species. The present review critically compiles and updates the available information on taxonomy, botanical description, distribution, traditional medicinal applications, phytochemistry, pharmacological activities, toxicity, and future research perspectives of Jatropha gossypifolia. This review highlights existing research gaps and emphasizes the need for standardized phytochemical characterization, mechanistic pharmacological studies, and well-designed clinical investigations to facilitate the development of evidence-based herbal therapeutics.