Excess copper (Cu) causes the toxic effects in plants and health hazards to humans. Therefore, in this study, the effect of sodium silicate (1 mM Si) and sodium nitroprusside (200 µM SNP as a releasing NO), was assessed on Cu tolerance in Salvia officinalis L. plants exposed to 400 µM CuSO4. Results revealed that the combined supplementation with Si and SNP rather than the single application of these chemicals lowered Cu concentrations and translocation factor and increased Mg, Zn, and Fe concentrations in roots and shoots. Furthermore, combined treatment more efficiently decreased electrolyte leakage enhanced the activities of POD and APX in the leaves and roots, and improved relative water content and the content of Chl. a and Chl. b in leaves and consequently further increased tolerance index. Silicon supply enhanced NO content and applying Si + SNP more than the treatment of Si alone increased Si concentrations in the roots and shoots under Cu stress. Therefore, the reciprocal interaction of Si and NO might enhance Cu tolerance in plants, and the combined application of Si and SNP might be a promising strategy to decrease heavy metal accumulation in medicinal plants grown in polluted lands.