Inflammation is a complex pathophysiological process associated with atherosclerosis, cancers, diabetes, osteoporosis, rheumatoid arthritis, cardiovascular and autoimmune diseases. In this review, we represent an overview of microbial-derived compounds, and nanomaterial with anti-inflammatory activity and compare their efficiency, mode actions, and limitations. This paper aims to provide an insight on possible approaches to expand the chemical space of anti-inflammatory drugs. The micro-based approach through the discovery of new anti-inflammatory compounds from microorganisms and nano-based approach through the augmentation by nanomaterials are among the main suggested natural and chemical resources to provide new anti-inflammation drugs in the future. Furthermore, some nanomaterials by improving the anti-inflammatory properties of commercial drugs or microbial compounds through enhancing their solubility, decreasing unfavorable effects, donating excellent targeting, allowing a lower dosage, and providing substitute less-invasive delivery routes, have shown their indirect anti-inflammatory activity. Additionally, the efficiency of existing drugs can also be modulated by using new synergistic anti-inflammatory compounds from microorganisms or modification/augmentation by nanomaterials. This will aid in designing new nano and bio-based medications for the prevention and treatment of numerous inflammation related-debilitating diseases.