Zinc oxide (ZnO) is a compound that has harmful effects as well as being used in many different areas. Numerous studies have been carried out to minimize the toxic effects of ZnO nanoparticles (NPs). In the present study, the protective role of resveratrol (RSV), a potent antioxidant polyphenol substance, was examined against ZnO-induced nanotoxicity on human pulmonary alveolar epithelial cells (HPAEpiC). In this context, the cytotoxic and genotoxic effects of different concentrations of RSV (5, 10, 20 mg/L) and ZnO NPs on the cells were measured alone and in combination. At the same time, the effects of aforementioned applications on the total antioxidant capacity (TAC) level in HPAEpiC were assessed. The results obtained showed that ZnO NPs alone significantly increased cytotoxicity and genotoxicity on cells compared to negative control (control (-)). In the experiments performed with RSV + ZnO NP combination, cytotoxic and genotoxic activity decreased at the level of p < 0.05 especially at 20 mg/L application of RSV. When the level of TAC in cells was examined, a concentration-dependent increase was detected between TAC and RSV. It was determined that ZnO NPs reduced the TAC level statistically (p < 0.05) in comparison with control (-). In conclusion, the present study revealed that RSV, a natural antioxidant, showed protective property against genotoxic and cytotoxic damage induced by ZnO NPs on HPAEpiC.