Background. Lepidium sativum (garden cress) is a member of the Brassicaceae family that has been utilized for medicinal and culinary purposes in centuries. Anti-inflammatory, antioxidant, immunomodulatory, hepatoprotective, antihypertensive, antiasthmatic, and hypoglycemic properties are found in various portions of the plant. The anti-inflammatory, antioxidant, and immunomodulatory effects of L. sativum were the subject of this review. Methods. The required information was gathered by searching the Web of Science, PubMed, and Scopus databases for the terms anti-inflammatory, antioxidant, immunomodulatory, immune system, and Lepidium sativum. Up until February 2022, the search was conducted. Results. TNF-, IL-6, IL-1, NO, iNOS, and HO-1 levels were reduced, indicating that L. sativum has anti-inflammatory and immunomodulatory properties. Flavonoids, alkaloids, cyanogenic glycosides, tannins, glucosinolates, sterols, and triterpenes are the key chemical components that contribute to the anti-inflammatory effects. In peritoneal neutrophils, L. sativum reduced oxidative stress by scavenging free radicals, as evidenced by a drop in superoxide anion and an increase in glutathione. Conclusion. The anti-inflammatory, antioxidant, and immunomodulatory activities of L. sativum could be explored in clinical trials to treat inflammatory and immune system illnesses.