Gas chromatography analysis of the essential oils of leaves and bark collected from the newly discovered tree Pleodendron costaricense identified alpha-pinene, beta-pinene, beta-myrcene, beta-thujene, and beta-caryophyllene as their major constituents. Phytochemical analysis of P. costaricense parts led to the isolation and identification of delta-tocotrienol, beta-sitosterol, four known drimane-type sesquiterpenes, cinnamodial ( 1), cinnamosmolide ( 2), polygodial ( 3), and mukaadial ( 4), and two new compounds, a drimane-type sesquiterpene, parritadial ( 5), and an eremophilane-type sesquiterpene, pleodendione ( 6). Antifungal assays with the two major compounds, 1 and 2, were carried out, and results showed a high activity of 1 against Alternaria alternata ( MIC) 3.9 mu g/mL), Candida albicans azole-resistant strain D10, and Wangiella dermatitides (MICs) 15.6 mu g/mL). Compound 2 showed less potent antifungal activities than 1 but was more effective against Candida albicans azole-resistant strain CN1A ( MIC) 23.4 mu g/mL) and Pseudallescheria boydii ( MIC) 78.1 mu g/mL). A combination of the dialdehyde sesquiterpenes with dillapiol showed a synergistic antifungal effect with 1 and an additive effect with 4 and 5.