Copper (Cu)-based pesticides have been widely used as a broad-spectrum management strategy in agriculture over the past century. However, extensive applications of conventional Cu-based pesticides over years can lead to Cu pollution and raise risks at the un-targeted organisms in the environment. A novel and sustainable strategy for improving the antimicrobial efficiency of pesticides while simultaneously minimizing their negative impacts on ecosystems is needed. Thus, this dissertation describes three main objectives to comprehensively understand the transformation of Cubased nanoparticles (NPs) as affected by root exudates in the rhizosphere, antifungal activity of newly developed Cu-based NPs, and their roles in the enhancement of nutrient uptake, metabolite regulation, and plant growth. 1) The effects of maize (Zea mays L.)-derived root exudates (RE) and their components on the aggregation and dissolution of copper oxide (CuO) NPs in the rhizosphere were investigated. In this work, RE significantly inhibited the aggregation of CuO NPs regardless of ionic strength and electrolyte type. Furthermore, this inhibition was correlated with the molecular weight (MW) of RE fractions. Higher MW fraction VII (>10 kDa) reduced the aggregation most. We also discovered that RE significantly promoted the dissolution of CuO NPs and lower MW fraction (< 3 kDa) RE mainly contributed to this process. The addition of 20 mg/L RE reduced the seedlings’ growth rate to 1.89% after 7 days of exposure to 25 mg/L CuO NPs, which were significantly lower than the control group (4.82%). Notably, Cu accumulation in plant root tissues was significantly enhanced by 20 mg/L RE. This study provides useful insights into the interactions between RE and CuO NPs, which is of significance for the safe use of CuO NPs-based antimicrobial products in agricultural production. 2) To increase the antifungal efficacy against the pathogenic activity of Gibberella fujikuroi (bakanae disease) in rice (Oryza sativa L.), we synthesized copper sulfide (CuS) NPs at 1: 1 and 1: 4 ratios of Cu and S, and treated infected rice (Oryza sativa L.) with CuS NPs by foliar application and seed treatment. The results showed that treating with both types of CuS NPs at 50 mg/L at the seed stage significantly decreased disease incidence on rice by 35.1 and 45.9%, respectively. Comparatively, CuO NPs achieved only 8.1% disease reduction, and the commercial Cu-based pesticide Kocide 3000 had no impact on disease. Foliar-applied CuO NPs and CuS (1: 1) NPs decreased disease incidence by 30.0 and 32.5%, respectively, which outperformed CuS (1: 4) NPs (15%) and Kocide 3000 (12.5%). Notably, CuS (1: 4) NPs also modulated the shoot salicylic acid (SA) and jasmonic acid (JA) production to enhance the plant defense mechanisms against G. fujikuroi infection. 3) The third study was aimed to investigate the effectiveness of a controlled release Cu-based nano-agrichemicals in control Fusarium oxysporum f. sp. lactucae (F.o. lact) infection on lettuce and explore their roles in the enhancement of nutrient uptake, VIII metabolite regulation, and plant growth. Our study demonstrated that as compared to commercial CuO NPs, the synthesized CuO NP-embedded hydrogels at 31 mg Cu/kg soil and 145 mg dried hydrogel powder/kg soil had a controlled release of Cu ions that could markedly reduce the required amounts of active components (e.g., Cu in this case). Additionally, compared to Kocide 3000 and CuO NPs, the synthesized CuO NPembedded hydrogels exhibited greater disease suppressing activity against F.o. lact. Notably, CuO NP-embedded hydrogels enhanced uptake of P, Mn, Zn, and Mg, and also increased the shoot levels of organic acids as compared to the diseased control. Increased SA but lowered levels of JA and abscisic acid (ABA) in shoots enhanced disease resistance.