This systematic review explores the therapeutic potential of bromelain, a mixture of proteolytic enzymes derived from pineapple (Ananas comosus). Bromelain has a long history of traditional medicinal use, particularly in Central and South America, where pineapple is native. The review delves into the history, chemical properties, and medical indications of bromelain, highlighting its multifaceted mechanisms of action, including anti-inflammatory, analgesic, antiangiogenic, and antioxidant properties. Bromelain's proteolytic activity aids in protein digestion and breaks down fibrin, promoting circulation. Its antioxidant effects involve scavenging free radicals and reactive oxygen species, while its immune modulatory effects enhance immune function and balance cytokine production. Bromelain also influences cell signaling pathways, such as PI3K/Akt and MAPK, and down-regulates plasma kininogen levels, inhibiting prostaglandin E2 expression. These properties make bromelain a promising candidate for treating various inflammatory and oxidative stress-related disorders. Clinical trials have demonstrated its efficacy and safety in conditions like osteoarthritis, sinusitis, surgical wounds, cardiovascular health, and digestive health. However, further research is needed to establish optimal dosing and treatment protocols. Bromelain is generally considered safe, with potential side effects including gastrointestinal disturbances and allergic reactions. The review also discusses bromelain's applications in aging, dermatology, infectious disorders, and cancer, emphasizing its potential in managing cellular senescence, wound healing, and enhancing the effectiveness of cancer treatments. Overall, bromelain's diverse therapeutic effects and potential benefits make it a valuable natural enzyme complex for various medical applications.This systematic review explores the therapeutic potential of bromelain, a mixture of proteolytic enzymes derived from pineapple (Ananas comosus). Bromelain has a long history of traditional medicinal use, particularly in Central and South America, where pineapple is native. The review delves into the history, chemical properties, and medical indications of bromelain, highlighting its multifaceted mechanisms of action, including anti-inflammatory, analgesic, antiangiogenic, and antioxidant properties. Bromelain's proteolytic activity aids in protein digestion and breaks down fibrin, promoting circulation. Its antioxidant effects involve scavenging free radicals and reactive oxygen species, while its immune modulatory effects enhance immune function and balance cytokine production. Bromelain also influences cell signaling pathways, such as PI3K/Akt and MAPK, and down-regulates plasma kininogen levels, inhibiting prostaglandin E2 expression. These properties make bromelain a promising candidate for treating various inflammatory and oxidative stress-related disorders. Clinical trials have demonstrated its efficacy and safety in conditions like osteoarthritis, sinusitis, surgical wounds, cardiovascular health, and digestive health. However, further research is needed to establish optimal dosing and treatment protocols. Bromelain is generally considered safe, with potential side effects including gastrointestinal disturbances and allergic reactions. The review also discusses bromelain's applications in aging, dermatology, infectious disorders, and cancer, emphasizing its potential in managing cellular senescence, wound healing, and enhancing the effectiveness of cancer treatments. Overall, bromelain's diverse therapeutic effects and potential benefits make it a valuable natural enzyme complex for various medical applications.