Most species of fungi are recognized as etiological agents from a vast number of human and animal diseases. Contrarily, in the Natural Products research field, it is considered a promising source of bioactive metabolites. The chemical diversity of fungi metabolism combined with potent biological activities might grant fungi metabolites to unearth new anti-inflammatory pharmacological therapies. On this basis, the pathological inflammation process is associated with several diseases, such as gout arthritis, autoimmune diseases, neurodegenerative disorders and several types of cancer. In the last 20 years, it was isolated from different Aspergillus strains anti-inflammatory metabolites with unique structural chemical patterns and high potency effect. Therefore, this systematic review aimed to identify the metabolites from members of the genus Aspergillus evaluated by anti-inflammatory assays as the main targets of pharmacological activity. From 231 anti-inflammatory metabolites that were descripted in this review, four exhibited high potential for multi-targeting inhibition. The current evidence demonstrates that the Aspergillus species are a rich source of compounds with significant anti-inflammatory properties that includes the alkaloids, butenolides, terpenoids and polyketides. In addition, an anti-inflammatory Aspergillus chemical database was built to support the chemical aspects of the review. Nevertheless, still, there is a lack of in vivo evaluations in the literature, and that is crucial to increase the knowledge about the mechanisms of actions of these fungal metabolites. Graphical Abstract: [Figure not available: see fulltext.] © 2021, Sociedade Brasileira de Farmacognosia.