Silymarin (SM) and its main constituent silibinin (SB) have been extensively studied for their anti-inflammatory properties. Inflammation is a vital defense mechanism, but when it becomes chronic, it leads to various diseases. SM/SB inhibit TLR4/NF-κB signaling and downregulate pro-inflammatory mediators like TNF-α, IL-1β, and IL-6. They also upregulate anti-inflammatory cytokines and lipid mediators involved in inflammation resolution. SM/SB have been shown to reduce inflammation in immune and non-immune cells, including macrophages, monocytes, epithelial cells, skin cells, bone cells, and cancer cells. In vivo studies demonstrate their protective effects in models of non-alcoholic fatty liver disease, toxicity, ischemia/reperfusion, stress-induced injuries, aging, and exercise. SM/SB reduce oxidative stress, inflammation, and tissue damage by modulating NF-κB, Nrf2, and other pathways. They also enhance antioxidant defenses and reduce pro-inflammatory cytokines. SM/SB have shown protective effects in various disease models, including liver toxicity, renal carcinogenesis, and neurodegenerative diseases. Their anti-inflammatory actions are attributed to their ability to suppress inflammatory responses and promote resolution of inflammation. SM/SB are important phytochemicals with potential health-promoting properties.Silymarin (SM) and its main constituent silibinin (SB) have been extensively studied for their anti-inflammatory properties. Inflammation is a vital defense mechanism, but when it becomes chronic, it leads to various diseases. SM/SB inhibit TLR4/NF-κB signaling and downregulate pro-inflammatory mediators like TNF-α, IL-1β, and IL-6. They also upregulate anti-inflammatory cytokines and lipid mediators involved in inflammation resolution. SM/SB have been shown to reduce inflammation in immune and non-immune cells, including macrophages, monocytes, epithelial cells, skin cells, bone cells, and cancer cells. In vivo studies demonstrate their protective effects in models of non-alcoholic fatty liver disease, toxicity, ischemia/reperfusion, stress-induced injuries, aging, and exercise. SM/SB reduce oxidative stress, inflammation, and tissue damage by modulating NF-κB, Nrf2, and other pathways. They also enhance antioxidant defenses and reduce pro-inflammatory cytokines. SM/SB have shown protective effects in various disease models, including liver toxicity, renal carcinogenesis, and neurodegenerative diseases. Their anti-inflammatory actions are attributed to their ability to suppress inflammatory responses and promote resolution of inflammation. SM/SB are important phytochemicals with potential health-promoting properties.