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One new dibenzocycloheptene, validinol (<b>1</b>), and one butanolide firstly isolated from the natural source, validinolide (<b>2</b>), together with 17 known compounds were isolated from the stem of <i>Cinnamomum validinerve</i>. Among the isolates, lincomolide A (<b>3</b>), secosubamolide (<b>7</b>), and cinnamtannin B1 (<b>19</b>) exhibited potent inhibition on both superoxide anion generation (IC₅₀ values of 2.98 ± 0.3 µM, 4.37 ± 0.38 µM, and 2.20 ± 0.3 µM, respectively) and elastase release (IC₅₀ values of 3.96 ± 0.31 µM, 3.04 ± 0.23 µM, and 4.64 ± 0.71 µM, respectively) by human neutrophils. In addition, isophilippinolide A (<b>6</b>), secosubamolide (<b>7</b>), and cinnamtannin B1 (<b>19</b>) showed bacteriostatic effects against <i>Propionibacterium acnes</i> in in vitro study, with minimal inhibitory concentration (MIC) values at 16 μg/mL, 16 μg/mL, and 500 μg/mL, respectively. Further investigations using the in vivo ear <i>P. acnes</i> infection model showed that the intraperitoneal administration of the major component cinnamtannin B1 (<b>19</b>) reduced immune cell infiltration and pro-inflammatory cytokines TNF-α and IL-6 at the infection sites. The results demonstrated the potential of cinnamtannin B1 (<b>19</b>) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan <i>C. validinerve</i> during bacterial infections.