Surface enhanced raman scattering (SERS) technique has been widely implemented for the detection/quantification of numerous compounds. The development of reusable SERS substrates through regeneration is a constant concern of scientists in the field, related to the sustainability of the method. Cold atmospheric plasma (CAP) is an advantageous green method well-known for its effectiveness towards the successful degradation of organic molecules and materials’ activation/modification. In the present study, we explored for the first time nanosecond pulsed dielectric barrier discharge (NSP-DBD) plasma as a rapid, energy efficient method for SERS solid substrates regeneration, implemented either directly in the gas or in the liquid phase as well as through immersion of the substrates in plasma activated water (PAW). We investigated the critical cold plasma factors (e.g. feeding gas, plasma treatment and retention time) in order to propose the most cost-effective alternative and shed light on the underlying regeneration mechanisms. The different SERS analysis case scenarios (analyte’s class , concentration andcross check) were considered, in order to simulate real SERS measurements conditions/requirements. In practical terms, such an approach will contribute to a significant reduction of the detection costs, revealing the NSP-DBD process as a flexible, fast, green, effective and low-cost solution towards the SERS substrates regeneration.