Yes there is good evidence that acetaminophen (the active ingredient in Tylenol) can deplete glutathione under certain conditions. But whether that matters depends on dose, duration, and individual factors. Sex differences in glutathione metabolism and acetaminophen toxicity Reducing the effects of drug toxicity on glutathione metabolism ScienceDirect g glutamyl cycle. Depletion of glutathione by acetaminophen leads to Download Scientific Diagram Glutathione Depletion in Mitochondrial Diseases Glutathione Reporter Sex differences in glutathione metabolism and acetaminophen toxicity