Potato (Solanum tuberosum L.) is a low-cost high-energy food possessing increasing demand around the world. Potato bacterial infections are serious biotic constraints to potato production, particularly in tropical and subtropical climates. This study aimed to manage Ralstonia solanacearum the causal agent of potato brown rot using salicylic acid (SA) and glycyrrhizic acid ammonium salt (GAS) in the colloidal and nano forms. SA and GAS were used in colloidal and nano form in three concentrations: 0.15, 0.30, and 1.25 mM to reduce the growth of the pathogen. Potato crop production and percentage of brown rot severity in Cara and Spunta cultivars were calculated. The gene expression profiles of Glucan endo-1,3-β-D-glucosidase, Polygalacturonase, Indole-3-acetic acid-amido synthetase GH3.3, and Cytoplasmic heat shock protein were assessed in Cara and Spunta cultivars under different treatments. The inhibition zone of Ralstonia solanacearum growth reached the highest record of 2.85 mm in response to 1.25 mM of GAS-NPs in comparison to other treatments. Interestingly, the treated Spunta cultivar with 1.25 mM recorded of 0% severity in comparison to 78.8% in the control. The Cara cultivar crop production increased to 4.62 kg in response to 1.25 mM SA-NPs compared to 3.72 kg, 3.9 kgs, and 1.82 kgs in the treated plants with 1.25 mM SA, negative and or positive control, respectively. GAS-NP treatments showed the lowest expression profile of plant defense genes and maintained the negative control expression profile. SA and GAS-NPs enhanced potato plant resistance and crop production in response to the phytopathogenic bacterial brown rot disease.