Chalcones, a class of flavonoid compounds characterized by their open-chain structure, have garnered significant interest in recent years due to their diverse biological activities, particularly their anti-inflammatory properties. This review article aims to highlight the current research on chalcones with a focus on their mechanisms of action in combating inflammation. By integrating findings from molecular, cellular, and clinical studies, this review highlights how chalcones modulate key inflammatory pathways, including the inhibition of proinflammatory cytokines, suppression of oxidative stress, and modulation of immune responses. Additionally, the article explores novel chalcone derivatives and their enhanced anti-inflammatory potentials, providing insights into their structure-activity relationships and therapeutic prospects. Through a comprehensive analysis, this review not only underscores the multifaceted roles of chalcones in inflammation management but also proposes future research directions to further elucidate their therapeutic efficacy and safety in clinical settings.