Fusarium graminearum invasion and Zearalenone (ZEN)-mycotoxin contamination are considered the most global threat to food and feed. This study investigates the effect Lactobacillus plantarum MON03 viable cells (LPVC) and LP free cells supernatant (LPFCS) against Fusarium graminearum growth and ZEN production in vitro and evaluates if treatment with LP viable cells can counteract the negative effect of ZEN on inflammation and oxidative stress in mesenteric lymph nodes and serum biochemical parameters in mice. For the in vitro study, 7 days of LPVC, LPFCS and F. graminearum co-incubation at different concentrations was done in order to determine the antifungal activity and ZEN- production inhibition. Regarding the in vivo study, Balb/c mice were treated as following: Control, ZEN group, LP group and ZEN + LP group for 30 days. In vitro, LPVC showed an excellent antifungal activity after 7 days of co-incubation (10 CFU/ml). LPVC was succeeded also to inhibit ZEN production by the fungi. In vivo, ZEN has shown an important oxidative damage. As a result of the exposure to ZEN, an increase cytokines, as effectors of an inflammatory response, were observed in the mesenteric lymph nodes (MLN) of intoxicated mice. In parallel, a serum biochemical change was also observed. LPVC induced a reduction of ZEN-induced oxidative stress and counteracts also the biochemical parameters damage and the inflammatory markers increased by ZEN. LPVC can be valorized as an anti-cating agent in the vitro and in the gastro-intestinal tract to decrease ZEN-toxic effects.