Safety is a prerequisite for foods, and most, if not all, of them exhibit no adverse effects under ordinary ingestion conditions. However, one may occasionally take them as supplements at high doses for the purpose of increasing their functions for health promotion and disease prevention. Therefore, it is meaningful to elucidate the molecular mechanisms underlying the adverse effects of food factors at high doses. For example, polyphenols with a catechol moiety and diallyl trisulfide have been shown to induce oxidative stress by generating reactive oxygen species via autoxidation and by reducing intracellular glutathione, respectively. In addition, electrophilic phytochemicals, which have catechol, α,β-unsaturated carbonyl, and isothiocyanate groups, may induce oxidative stress and proteostress via electrophilic addition to the cysteine and lysine residues of cellular proteins. In this chapter, the author exemplified the adverse effects of food factors at high doses, which were reported from cellular, rodent, and clinical studies, and addressed their potential mechanisms of harmful action.