Recent advances in anti-inflammatory effects via AMPK activation are reviewed, highlighting the role of AMPK in regulating inflammation and metabolic diseases. AMPK, a key energy sensor, modulates cellular energy homeostasis and glycolipid metabolism. It inhibits NF-κB, reduces inflammatory gene expression, and suppresses inflammatory damage. SIRT1, a deacetylase, is regulated by AMPK and plays a role in energy balance and inflammation. AMPK activation also inhibits the NLRP3 inflammasome, reducing inflammatory responses. Lactone compounds like melatonin activate AMPK and SIRT1, balancing Th17/Treg cells and reducing oxidative stress in necrotising enterocolitis (NEC). Corosolic acid (CA) and ilexgenin A (IA) inhibit inflammation through AMPK/SIRT1 and NLRP3 pathways, reducing ER stress and improving endothelial function. Cryptotanshinone (CT) suppresses inflammation by inhibiting NF-κB and activating AMPK/SIRT1, reducing ethanol-induced liver injury. Sesquiterpene lactones, such as Atractylenolide III, reduce inflammation by activating AMPK/SIRT1 and restoring mitochondrial function. Polyphenols like quercetin, isovitexin, nobiletin, luteolin, dihydromyricetin, baicalin, and mangiferin inhibit inflammation through AMPK activation, reducing oxidative stress and NLRP3 inflammasome activity. Curcumin and resveratrol suppress inflammation by activating AMPK and reducing inflammatory markers. Pterostilbene and magnolol/honokiol also exhibit anti-inflammatory effects via AMPK and Nrf2 pathways. These compounds show potential in treating inflammatory diseases, metabolic disorders, and cancer by modulating AMPK and related pathways. Further research is needed to optimize their therapeutic applications.Recent advances in anti-inflammatory effects via AMPK activation are reviewed, highlighting the role of AMPK in regulating inflammation and metabolic diseases. AMPK, a key energy sensor, modulates cellular energy homeostasis and glycolipid metabolism. It inhibits NF-κB, reduces inflammatory gene expression, and suppresses inflammatory damage. SIRT1, a deacetylase, is regulated by AMPK and plays a role in energy balance and inflammation. AMPK activation also inhibits the NLRP3 inflammasome, reducing inflammatory responses. Lactone compounds like melatonin activate AMPK and SIRT1, balancing Th17/Treg cells and reducing oxidative stress in necrotising enterocolitis (NEC). Corosolic acid (CA) and ilexgenin A (IA) inhibit inflammation through AMPK/SIRT1 and NLRP3 pathways, reducing ER stress and improving endothelial function. Cryptotanshinone (CT) suppresses inflammation by inhibiting NF-κB and activating AMPK/SIRT1, reducing ethanol-induced liver injury. Sesquiterpene lactones, such as Atractylenolide III, reduce inflammation by activating AMPK/SIRT1 and restoring mitochondrial function. Polyphenols like quercetin, isovitexin, nobiletin, luteolin, dihydromyricetin, baicalin, and mangiferin inhibit inflammation through AMPK activation, reducing oxidative stress and NLRP3 inflammasome activity. Curcumin and resveratrol suppress inflammation by activating AMPK and reducing inflammatory markers. Pterostilbene and magnolol/honokiol also exhibit anti-inflammatory effects via AMPK and Nrf2 pathways. These compounds show potential in treating inflammatory diseases, metabolic disorders, and cancer by modulating AMPK and related pathways. Further research is needed to optimize their therapeutic applications.