Fusarium Head Blight (FHB) of small-grain cereals such as wheat and barley and Gibberella Ear Rot (GER) of maize are two devastating fungal diseases affecting crops worldwide. Both FHB and GER are primarily caused by Fusarium graminearum in Europe. In addition to direct losses related to yield reduction, F. graminearum poses potential health risks to animals and humans due to the production of type B trichothecene (TCTB) mycotoxins. The development of environmental-friendly strategies guaranteeing the safety of food and feed is a key challenge facing agriculture today. One of these strategies lies on the promising capacity of products issued from natural sources to counteract crop pests. In these works, the in vitro efficiency of extracts obtained from wood/forest and vine byproducts using both classical and subcritical water extractions was assessed against fungal growth and TCTB production by a panel F. graminearum strains. Maritime pine sawdust and vine root extracts were shown to be extremely efficient, leading to a significant inhibition higher than 90% of the fungal growth and a higher than 65% reduction of the mycotoxin production by F. graminearum. High-resolution LC-MS/MS analysis of natural active extracts revealed the presence of several families of phenolics with a predominance of methylated compounds and suggested that the abundance of these structures, and therefore of hydrophobic compounds, could be a primary factor underpinning the activity of the natural extracts. In addition, a bioactivity molecular networking strategy applied to the LC-MS/MS data of the extracts allowed us to suggest that oligomeric phenolic structures are the active molecules. These hypotheses are currently being tested using a biofractionation strategy and in vitro assays with pure molecules. Altogether, our data support that wood/forest and vine by-products could be promising sources of bioactive compounds for controlling F. graminearum and its production of mycotoxins.