Obesity is one of the important causative factors leading to various metabolic diseases such as insulin resistance, diabetes, cardiovascular disease, and fatty liver. The development of novel therapeutic targets, mechanisms and safe, effective anti-obesity agents remains an urgent scientific challenge. In recent years, several promising strategies have emerged, including suppression of chronic low-grade inflammation, modulation of appetite-regulating pathways, induction of white adipose tissue browning and thermogenesis, inhibition of lipase activity and de novo lipogenesis, and regulation of gut microbiota composition. Natural products, particularly bioactive compounds derived from dietary sources, have garnered significant attention due to their multi-target pharmacological effects, favorable safety profiles, and potential for long-term use. This comprehensive review summarizes over 80 natural small molecules reported in recent years, focusing on their role in promoting adipose remodeling, enhancing lipids metabolism, attenuating metabolic inflammation, and restoring gut microbial homeostasis. We aim to provide valuable insights for the development of next generation anti-obesity drugs and functional food supplements.