Zinc oxide nanoparticles (ZnO NPs) can possibly serve as a pervasive source of essential nutrient zinc in agricultural crops in the future. The major environmental concerns with ZnO NPs might be their toxicity and incorrect dosage, which might lead to crop damage and environmental pollution. Interplay between ZnO NPs and Lactuca sativa (L. sativa) will be of interest, yet little is known about apropos interaction of these two, which will assist in optimizing the dose of ZnO NPs for their commercial use in agriculture. The current study aimed to investigate the growth, anatomical, and antioxidative responses of L. sativa against ZnO NPs and zinc acetate. ZnO NPs were foliar sprayed with concentrations of 0, 25, 50, and 100 ppm. ZnO NPs remarkably promoted L. sativa growth, leaf water content, and biomass accumulation; however, they declined root growth. The foliar spray of ZnO NPs improved the thickness of the stem hypodermis, cortex, pericycle, and phloem, while decreasing the stem diameter, thickness of the epidermis, and number of vascular bundles. ZnO NPs rigorously declined the cell area of xylem but slightly improved it in phloem. Unlike stem cells’ anatomical responses to ZnO NPs, the root cells behaved otherwise. Overall, the antioxidative activity of L. sativa considerably improved at 25 ppm concentration and decreased at 100 ppm. Generally, low and medium concentrations of ZnO NPs promoted plant morphological, anatomical, and antioxidant traits, while higher doses inhibited the same traits. Contrary to this, Zn acetate displayed severe toxic effects on almost all studied anatomical traits
