Glutathione is an important biological free radical scavenger, aiding in the prevention of oxidative stress in living organisms. A decrease in glutathione concentration in cells or bodily fluids is associated with serious health issues including certain cancers and Alzheimer's disease. Rapid detection and quantification of salivary glutathione could play a crucial role in healthcare monitoring as well as in therapeutic progress. This paper reports on the development of a direct electrochemical surface-enhanced Raman spectroscopic (EC-SERS) method for the monitoring of glutathione deposited via drop casting from a prepared aqueous stock solution and measured in 0.1-M sodium fluoride and in artificial saliva. The detection platform for this study is constructed by modifying the working electrode of a carbon screen-printed electrode with silver nanoparticles of approximately 30 nm in diameter, followed by potassium chloride treatment to remove interfering citrate anions prior to analysis. The coupling of SERS and an applied electrochemical potential resulted in a significantly enhanced spectrum for glutathione compared with those previously reported. Vibrational mode assignment confirmed that glutathione was indeed in close proximity to the surface of the working electrode and had varying anchor points as the potential was stepped anodically. Quantitative analysis of glutathione in artificial saliva showed that the 653 cm À1 marker peak intensity varies linearly (R 2 = 0.990) over the concentration of 0.005-1.00 mM on the modified electrode surface. The signal limit of detection of glutathione using EC-SERS in artificial saliva was determined to be 5 μM. This direct and rapid EC-SERS detection platform is promising for point-of-care diagnostics.Electronic Supplementary Information (ESI) available: Experimental details Including electrochemical surface-enhanced Raman spectroscopic spectra of all concentrations of GSH and in saliva at different pH as discussed and calculations for the LoD of glutathione (PDF). See