Incorporating nanoparticles into plant cultivation has been shown to improve growth parameters and alter the bioactive component compositions of many plant species, includingCurcumin longa. The aim of the current study was to investigate the effects of foliar application of zinc oxide nanoparticles on the content of bioactive compounds and their antibacterial activities against potential bacterial pathogens. To this end,C. longaleaves were treated with different doses of ZnO NPs to see how this affected their bioactive component composition. The effect of different doses of ZnO NPs on the accumulation of bisdemethoxycurcumin, demethoxycurcumin, and curcumin in ethanolic extracts ofC. longarhizomes was evaluated using high-performance liquid chromatography (HPLC). When compared to the control treatment, foliar spraying with (5 and 40 mgL−1) of ZnO NPs increased bisdemethoxycurcumin, demethoxycurcumin, and curcumin levels approximately (2.69 and 2.84)-, (2.61 and 3.22)-, and (2.90 and 3.45)-fold, respectively. We then checked whether the ethanolic extracts produced from the plantlets changed in terms of their phytochemical makeup and antibacterial properties. Furthermore, the results revealed thatC. long-ZnO NPs displayed antibacterial activity against the testedS. aureusandP. aeruginosabacterium strains, but had a few effect againstE. coli.The MIC forP. aeruginosawas 100 g/mL. The time–kill studies also revealed that ZnO NPs at 4 MIC killedP. aeruginosa,Actinobacteria baumannii, andBacillussp. after 2 h, whileS. aureusdid not grow when treated with 4 × MIC of the extract for 6 h. The strongest antibacterial activity was seen in the extract from plantlets grown without nanoparticles forP. aeruginosa, whereas it was seen in the extract from plantlets grown in the presence of 5 mg/L ZnO NPs forE. coli,S. aureus, andP. aeruginosa. These findings show that ZnO NPs are powerful enhancers of bioactive compound production inC. longa,a trait that can be used to combat antibiotic resistance in pathogenic bacterial species.