Zinc oxide nanoparticles (ZnO-NPs) have been proven to helpfully improve plant tolerance to several abiotic stresses. However, no information has been reported concerning the role of ZnO-NPs on pepper plants under salinity stress. Hence, this research aimed to evaluate the growth and physiological responses of pepper (Capsicum annum L.) plants to ZnO-NP foliar application under salinity. Plants were subjected to 0 (control), 25 (S1), 50 (S2), and 75 mM (S3) NaCl salinity with a foliar spray of 0, 1000, and 2000 ppm ZnO-NPs. Significant reductions were recorded in the chlorophyll index (SPAD) and chlorophyll fluorescence parameters, and in the activity and/or ratios of reduced ascorbate (AsA), reduced ascorbate/dehydroascorbic acid (AsA/DHA), reduced glutathione (GSH), reduced glutathione/oxidized glutathione (GSH/GSSG), and K+ content. There was a significant increase in proline content, electrolyte leakage (EL), H2O2 content, guaiacol peroxidase (GPX), ascorbate peroxidase (APX), superoxide dismutase (SOD), glutathione reductase (GR), dehydroascorbic acid (DHA), and oxidized glutathione (GSSG) activities, and in Na+ content and Na+/K+ ratio. Foliar treatments improved the salinity tolerance of the pepper plants by fortifying the antioxidant defense system, leaf fluorescence parameters, K+, and proline content, and in contrast, by decreasing the EL, Na+, and H2O2 levels. ZnO-NP foliar treatment efficiently improved the pepper plants’ physiological responses under salinity. Considering the overall results, 1000 ppm of ZnO-NPs would be advisable for the amelioration of salinity depression and to promote growth potential. However, at higher levels, the nanoparticle showed toxicity symptoms that limited its reliable applications.