In recent years, marine natural products (MNPs) have emerged as crucial sources of lead compounds for the advancement of anti-inflammatory drugs due to their abundant diversity, complexity, and distinctiveness. Inflammatory microenvironments (IMEs) are pervasive pathological features in the etiology of various chronic diseases, referring to the localized milieu or ecosystem where inflammatory responses occur, and they play a pivotal role in the onset and progression of inflammatory diseases. Uncontrolled IMEs can lead to dysregulation of inflammatory mediators within signaling pathways, thereby exerting detrimental effects on human health and even contributing to the development of inflammatory diseases such as cancer. Currently, inflammation treatment predominantly relies on chemical drugs. Nevertheless, these existing therapies are constrained by their numerous side effects and slow remission of symptoms. Consequently, there is an urgent need for the discovery and development of new drugs that exhibit minimal side effects while exerting potent anti-inflammatory effects. This article extensively explored the activities and mechanisms of MNPs (covering studies from 2010 to 2024) regulating key signaling pathways and inflammatory mediators in the IME, which establishes a theoretical basis for the further development of anti-inflammatory drugs.