Mycotoxins are toxic fungal metabolites, contaminating cereal grains in field or during processing and storage periods. These environmental contaminants pose great threats to humans and animals’ health due to their toxic effects. Type A trichothecenes, fumonisins and fusaric acid (FA) are commonly detected mycotoxins produced by various Fusarium species. Trichoderma spp. are promising antagonists in agriculture for their activities against plant pathogens, and also regarded as potential candidates for bioremediation of environmental contaminants. Managing toxigenic fungi by antagonistic Trichoderma is regarded as a sustainable and eco-friendly strategy for mycotoxin control. However, the metabolic activities of Trichoderma on natural occurring mycotoxins were less investigated. Our current work comprehensively explored the activities of Trichoderma against type A trichothecenes, fumonisins and FA producing Fusarium species via co-culture competition and indirect volatile assays. Furthermore, we investigated metabolism of type A trichothecenes and FA in Trichoderma isolates. Results indicated that Trichoderma were capable of bio-transforming T-2 toxin, HT-2 toxin, diacetoxyscirpenol and neosolaniol into their glycosylated forms and one Trichoderma strain could bio transform FA into low toxic fusarinol. These findings proved that Trichoderma isolates could manage toxigenic Fusarium via direct competition and volatile-mediated indirect inhibition. In addition, these antagonists possess defensive systems against mycotoxins for self-protection, which enriches our understanding on the interaction mechanism of Trichoderma spp. on toxigenic fungus.