Due to some important applications of guanine electrode in scientific and technology research such as electro-chemical DNA based biosensors, and a problem of high redox potential of guanine (0.81 V), our research study concentrates on reducing guanine redox potential by substituting Cu, Ag, Au, CH3, C2H5 and Cl on sites of 1, 2 and 9 of guanine. A 5.0% reduction of redox potential for 9-Ag-guanine was the sign of favorable result. In order to have further lower potential, sliver clusters (Ag2 andAg3) were used. The obtained percentages of reduction of potentials were 53.6% and 36.8% for 9-Ag2 and 9-Ag3-guanine, respectively. In this research, Gaussian 09 was used and DFT was applied with long-range corrected xc-functional (LC-BLYP).