Nano-fertilizers with higher efficacy compared to conventional fertilizers can provide advantage for plant cultivation in both productive and problematic soils. Therefore, this study aimed to determine the effect of nano-calcium (nano-Ca) on lettuce plants grown in saline-boron toxic soil. Nano-calcium fertilizer was prepared from eggshells. Functional and structural properties of nano-Ca was determined by scanning electron microscopy (SEM), x-ray diffraction (XRD) and fourier transform infrared spectroscopy (FTIR) before plant experiment. The treatments was; control, 40 mM NaCl and 20 mg kg−1 B (NaCl + B), and 40 mM NaCl and 20 mg kg−1 B with 4 mM Nano-Ca (NaCl + B + nano-Ca). The nano-Ca significantly increased the dry weight and calcium (Ca) concentration of lettuce plants under saline-B toxic conditions. Although there was a decrease in the concentrations of sodium (Na), chloride (Cl), and boron (B) with nano-Ca treatment, it was not statistically significant. Salinity and boron toxicity lead to increased lipid peroxidation. In the present study, the production of malondialdehyde (MDA) as a marker for lipid peroxidation, along with a significant decrease in hydrogen peroxide (H2O2) concentration, was observed with the application of nano-Ca. There was no significant alteration in superoxide dismutase activity (SOD) observed in lettuce grown under saline and boron toxic conditions. However, catalase activity (CAT) increased with nano-Ca application, while the activity of ascorbate peroxidase (APX) decreased. The study results suggest that nano-Ca serves a protective function for lettuce plants cultivated under saline and boron toxic conditions.