Organic biostimulators support wheat growth in unfavorable conditions; however, to date, multifactorial assessments of their role in the plant–pesticide–pathogen system have been poorly investigated. The goal of this study was to evaluate the changes in the metabolite profile (protein, carbohydrate, phenolic compounds, acid phosphatases, and amino acids) and the antioxidant potential (antioxidant enzymes) of wheat that is infested with F. culmorum and exposed to humic acids, nitrophenols, and six pesticides. Additionally, the concentration of the mycotoxins in the wheat grain and the dissipation time of the six pesticides in the wheat plants were determined. In this multifactorial experiment, we explored differentiated activities of humic acids and nitrophenols in wheat metabolism during fungal pathogenesis and pesticide protection. Nitrophenols decreased oxidative stress through induced catalase activity. In contrast, humic acids contributed to the highest enhancement of the total level of carbohydrates (27%) in the inoculated wheat. Both biostimulators reduced the mycotoxin concentration (DON, 3-AcDON, 15-AcDON, NIV) by 32% and nitrophenols increased the concentration of amino acids (13%). Unexpectedly, humic acids and nitrophenols shortened the degradation time (DT₅₀) of spiroxamine by up to 60% in inoculated wheat. The overall results of this study provide novel information on the changes in wheat metabolites, antioxidant defense, and pesticide dissipation in the pesticide–biostimulator–pathogen system.