Bromelain is a proteolytic enzyme complex derived from pineapple (Ananas comosus), with a long history of traditional use in various cultures, particularly in Central and South America. This review explores the history, structure, chemical properties, and medical applications of bromelain. First isolated in the late 19th century, bromelain has been widely used in both traditional and modern medicine for its therapeutic potential. It is now produced in several countries, including Taiwan, Thailand, Brazil, and Puerto Rico, and has found commercial applications as a meat tenderizer and a nutraceutical. However, its complex composition has posed challenges for pharmaceutical development. Bromelain exhibits a range of biological activities, including proteolytic activity, anti-inflammatory effects, antioxidant properties, immune modulation, and fibrinolytic activity. These properties contribute to its potential therapeutic applications in various medical conditions, such as inflammation, edema, digestive health, aging, dermatology, infectious disorders, and cancer. Clinical trials have demonstrated its efficacy and safety in conditions like osteoarthritis, sinusitis, and digestive health. However, more research is needed to confirm these findings and establish optimal dosing regimens. Bromelain's anti-inflammatory effects are attributed to its ability to inhibit the production of inflammatory mediators, including cytokines, prostaglandins, and leukotrienes. It also modulates the nuclear factor-kappa B (NF-κB) signaling pathway, reducing inflammatory gene expression. Additionally, bromelain has been shown to inhibit the expression of COX-2, thereby reducing the production of prostaglandin E2 (PGE2), a key mediator of inflammation and pain. In dermatology, bromelain is used for its anti-inflammatory and wound-healing properties, and it has been explored for its potential in treating skin conditions. In infectious disorders, bromelain exhibits antibacterial properties and may help prevent wound infections. Recent studies suggest that bromelain may have potential in treating viral infections, including COVID-19, by disrupting viral proteins and inhibiting viral entry. In cancer research, bromelain has shown potential in inhibiting tumor growth, preventing metastasis, and enhancing the effectiveness of chemotherapy. Its proteolytic activity may contribute to the inhibition of cancer cell proliferation and the induction of apoptosis. Additionally, bromelain may modulate the immune system, enhancing immune function and potentially improving the body's defense against infections. Overall, bromelain is a natural enzyme complex with diverse therapeutic potential, and further well-designed clinical trials are needed to elucidate its mechanisms of action, optimal dosing regimens, and efficacy in various medical conditions.Bromelain is a proteolytic enzyme complex derived from pineapple (Ananas comosus), with a long history of traditional use in various cultures, particularly in Central and South America. This review explores the history, structure, chemical properties, and medical applications of bromelain. First isolated in the late 19th century, bromelain has been widely used in both traditional and modern medicine for its therapeutic potential. It is now produced in several countries, including Taiwan, Thailand, Brazil, and Puerto Rico, and has found commercial applications as a meat tenderizer and a nutraceutical. However, its complex composition has posed challenges for pharmaceutical development. Bromelain exhibits a range of biological activities, including proteolytic activity, anti-inflammatory effects, antioxidant properties, immune modulation, and fibrinolytic activity. These properties contribute to its potential therapeutic applications in various medical conditions, such as inflammation, edema, digestive health, aging, dermatology, infectious disorders, and cancer. Clinical trials have demonstrated its efficacy and safety in conditions like osteoarthritis, sinusitis, and digestive health. However, more research is needed to confirm these findings and establish optimal dosing regimens. Bromelain's anti-inflammatory effects are attributed to its ability to inhibit the production of inflammatory mediators, including cytokines, prostaglandins, and leukotrienes. It also modulates the nuclear factor-kappa B (NF-κB) signaling pathway, reducing inflammatory gene expression. Additionally, bromelain has been shown to inhibit the expression of COX-2, thereby reducing the production of prostaglandin E2 (PGE2), a key mediator of inflammation and pain. In dermatology, bromelain is used for its anti-inflammatory and wound-healing properties, and it has been explored for its potential in treating skin conditions. In infectious disorders, bromelain exhibits antibacterial properties and may help prevent wound infections. Recent studies suggest that bromelain may have potential in treating viral infections, including COVID-19, by disrupting viral proteins and inhibiting viral entry. In cancer research, bromelain has shown potential in inhibiting tumor growth, preventing metastasis, and enhancing the effectiveness of chemotherapy. Its proteolytic activity may contribute to the inhibition of cancer cell proliferation and the induction of apoptosis. Additionally, bromelain may modulate the immune system, enhancing immune function and potentially improving the body's defense against infections. Overall, bromelain is a natural enzyme complex with diverse therapeutic potential, and further well-designed clinical trials are needed to elucidate its mechanisms of action, optimal dosing regimens, and efficacy in various medical conditions.