Six new (1-6), together with seven known (7-13), trichothecenes were isolated from the soil-derived Trichoderma brevicompactum PSU-RSPG27. Their structures were established using spectroscopic data. The structure of 1 was confirmed by X-ray data. Trichodermin (7) exhibited the most potent activity against Plasmodium falciparum (K1 strain) with an IC<sub>50</sub> value of 0.1 μM, while other trichothecenes (1, 8, 9, and 12) were much less active, with IC<sub>50</sub> values in the range of 7.1-9.6 μM. Compound 7 displayed activity against noncancerous Vero cells with an IC<sub>50</sub> value of 0.4 μM. The remaining compounds showed moderate to weak activity, with IC<sub>50</sub> values in the range of 6.9-15.3 μM. Compounds 7 and 12 were active against human oral carcinoma (KB) cells with IC<sub>50</sub> values of 2.4 and 3.7 μM, respectively. Additionally, compounds 7 and 12 displayed antifungal activity against Candida albicans with the respective MIC values of 1 and 2 μg/mL and were active against Cryptococcus neoformans with equal MIC values of 4 μg/mL.