Fusarium oxysporum f.sp. lycopersici (FOL) wilt endangers Egyptian tomato productivity. Nanotechnology has emerged as an efficient tool for managing plant diseases. This study evaluated salicylic acid nanoparticles (SA-NPs) and glycyrrhizic acid ammonium salt nanoparticles (GAS-NPs) against F. oxysporum in vitro. SA-NPs reduced F. oxysporum growth by 37.8%, and GAS-NPs by 18.9% at 3 ml/L, while SA-NPs at high doses significantly reduced the bacterial count in the tomato rhizosphere. Under greenhouse conditions, high doses of SA-NPs suppressed disease by 73%, compared to 87-93% for other treatments, coinciding with a significant decrease in the overall bacterial count in the tomato rhizosphere. A high dose of SA-NPs reduced heterotrophic, copiotrophic, and fluorescent pseudomonads in the tomato rhizosphere but did not affect the total number of fungi. In vitro, a high dose of both nanoparticles did not significantly reduce bacterial growth in four tested strains: Leclercia adecarboxylata, Pseudomonas putida, Enterobacter ludwigii, and Bacillus marcorestinctum. This suggests that while SA-NP doesn't directly affect bacterial growth, it may interact with tomato roots, indirectly affecting the rhizosphere bacterial population. All treatments increased the expression of ethylene-responsive transcription factor 3 (RAP), xyloglucan endotransglucosylase 2 (XET-2), catalytic hydrolase-2 (ACS-2), phenylalanine ammonia-lyase 5 (PAL5), lipoxygenase D (LOXD), proteinase inhibitor II (PINII), and pathogenesis-related protein 1 (PR1). The highest gene expression levels were obtained from 1 ml/L GAS-NPs and SA-NPs field applications. Furthermore, SA-NPs at 1 ml/L were the most efficient in controlling tomato Fusarium wilt, followed by GAS-NPs. This study investigates the possibility of nanotechnology-based techniques for decreasing Fusarium wilt in tomatoes. However, because of the deleterious impact on the soil bacterial community, high dosages of NPs, particularly SA-NPs, should be applied with caution. Future research should focus on optimizing NPs doses to maintain a balance between efficient disease control and the maintenance of the beneficial complexity of soil microbial biodiversity.