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It is reported that various fungi have been used for medicine and edible foods. The tropical <i>Trametes</i> genus is popular and well-known in Vietnam for its health effects and bioactivities. In this study, the fruiting bodies of the edible fungi <i>T. cubensis</i> and <i>T. suaveolens</i> were collected in Vietnam. The preliminary bioactivity screening data indicated that the methanol extracts of the fruiting bodies of <i>T. cubensis</i> and <i>T. suaveolens</i> displayed significant inhibition of superoxide anion generation and elastase release in human neutrophils. Therefore, the isolation and characterization were performed on these two species by a combination of chromatographic methods and spectrometric analysis. In total, twenty-four compounds were identified, and among these (<b>1–3</b>) were characterized by 1D-, 2D-NMR, and HRMS analytical data. In addition, the anti-inflammatory potentials of some purified compounds were examined by the cellular model for the inhibition of superoxide anion generation and elastase release in human neutrophils. Among the isolated compounds, (<b>5</b>,<b>14</b>), and (<b>19</b>) displayed significant anti-inflammatory potential. As the results suggest, the extracts and isolated compounds from <i>T. cubensis</i> and <i>T. suaveolens</i> are potential candidates for the further development of new anti-inflammatory lead drugs or natural healthy foods.