Inflammation is the body’s self-protective response to multiple stimulus, from external harmful substances to internal danger signals released after trauma or cell dysfunction. Many diseases are considered to be related to inflammation, such as cancer, metabolic disorders, aging, and neurodegenerative diseases. Current therapeutic approaches include mainly non-steroidal anti-inflammatory drugs and glucocorticoids, which are generally of limited effectiveness and severe side-effects. Thus, it is urgent to develop novel effective anti-inflammatory therapeutic agents. Xanthones, a unique scaffold with a 9H-Xanthen-9-one core structure, widely exist in natural sources. Till now, over 250 xanthones were isolated and identified in plants from the families Gentianaceae and Hypericaceae. Many xanthones have been disclosed with anti-inflammatory properties on different models, either in vitro or in vivo. Herein, we provide a comprehensive and up-to-date review of xanthones with anti-inflammatory properties, and analyzed their drug likeness, which might be potential therapeutic agents to fight against inflammation-related diseases.