Mangrove‐derived actinomycetes are prolific chemical sources of complex and novel natural products, providing an excellent chance for new drug discovery. The chemical investigation of the mangrove‐derived Streptomycessundarbansensis 06037, led to the discovery of two previously undescribed enone fatty acids (1‐2), one new phenylpropionate derivate (3), along with the isolation of the ten known components (4‐13). Those chemical structures of isolates were elucidated on the basis of the analysis of diverse spectroscopic data. Initial anti‐inflammatory tests of 1‐3 in lipopolysaccharide (LPS)‐activated RAW 264.7 murine macrophage cells revealed that compound 1 possess significant inhibitory effect on the production of Nitro oxidase (NO), with the IC50 value around 15.33 ± 1.32 μM, together with the suppression of NF‐κB phosphorylation and reducing the release of oxygen species (ROS) in RAW 264.7 macrophages, those results indicated that compound 1 may exert its anti‐inflammatory activity through a reduction in ROS level and the suppression of NF‐κB activation pathway.