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. Acetaminophen metabolism Electrochemical evidences in oxidation of acetaminophen in the presence of glutathione and N acetylcysteine Chemical Communications (RSC Publishing) Glutathione: Master Antioxidant, Reducing Oxidative Stress, and Detoxification The gamma glutamyl pathway after glutathione depletion due to Download Scientific Diagram