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The genus <i>Cotula</i> (Asteraceae) comprises about 80 species, amongst them <i>Cotula anthemoides</i> L. It is a wild plant growing in Egypt that possesses many traditional uses as a headache, colic, and chest cold remedy. In our study, the chemical composition of <i>C</i>. <i>anthemoides</i> essential oils was analyzed using GC-MS spectroscopy. Sixteen components of leave and stem oils and thirteen components of flower oils were characterized. The main components in both essential oil parts were camphor (88.79% and 86.45%) and <i>trans</i>-thujone (5.14% and 10.40%) in the leaves and stems and the flowers, respectively. The anti-inflammatory activity of the oils in lipopolysaccharide-stimulated RAW 264.7 macrophage cells was evaluated. The flower oil showed its predominant effect in the amelioration of proinflammatory cytokines and tumor necrosis factor-α, as well as cyclooxygenase-2. The bornyl acetate showed the highest affinity for the cyclooxygenase-2 receptor, while compound <i>cis</i>-<i>p</i>-menth-2-ene-1-ol had the best affinity for the tumor necrosis factor receptor, according to the results of molecular docking. In addition, the molecule <i>cis</i>-<i>β</i>-farnesene showed promising dual affinity for both studied receptors. Our findings show that essential oils from <i>C</i>. <i>anthemoides</i> have anti-inflammatory properties through their control over the generation of inflammatory mediators. These findings suggest that <i>C</i>. <i>anthemoides</i> essential oils could lead to the discovery of novel sources of anti-inflammatory treatments.