Herein we study the electrochemical potential-dependent and time-dependent stability of thiols and disulfides as self-assembled monolayers on gold electrodes. The stability of four representative sulfur-containing compounds: 3-mercaptopropionic acid, 2-mercaptoethanol, 1,4-dithiothreitol and DL-thioctic acid, was assessed in simulated physiological conditions (Le. phosphate buffer saline). The stability of these molecules was evaluated using cyclic voltammetry and step-potential chronoamperometry. Coordination of the thiols and disulfides significantly affects the stability of the self-assembled monolayer. In addition, studies performed using gold single crystal (100) and (111) electrodes show the superior binding strength of the SAM on the Au(100) surface structure.