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. Tylenol's Impact on Glutathione and Liver Damage Liver injury induced by paracetamol and challenges associated with intentional and unintentional use The Protective Effects of Garlic Extract Against Acetaminophen Induced Oxidative Stress and Glutathione Depletion