Background: Acrylamide (AA), a product formed from fried foods, has been recognized as a genotoxic agent in animals and humans. Oxidative stress is considered as an indirect cause of AA-related genotoxicity. Objective: Resveratrol (RES) (trans-3,4′,5-trihydroxystilbene) is a natural polyphenol produced by plants such as grapes, berries, and peanuts. In the present work, we studied the potential positive effect of RES in preventing oxidative stress-related cytotoxicity and genotoxicity induced by AA in vitro using rat primary lymphocyte cells. Materials and Methods: The primary lymphocyte cells were induced with AA (5–500 mg/L) for toxicological evaluation and pretreated with RES (100 μM) to determine its protective effect on AA-induced toxicity. The reactive oxygen species (ROS), an inference of oxidative stress, the antioxidant enzyme activity of catalase (CAT), superoxide dismutase (SOD) and glutathione S-transferase (GST) were measured. In addition, the micronucleus (MN) and nuclear fragmentation were analyzed by confocal microscopy to study the protective role of RES on AA-induced genotoxicity. Results: The cells pretreated with RES at a concentration of 100 μM for 24 h protected against AA-induced cytotoxicity, caused a reduction in ROS, showed an elevation in the activity of CAT, SOD, and GST signifying an increase in antioxidant function. Furthermore, the genotoxic effects of DNA damage, MN and nuclear fragmentation induced by AA were reduced on RES preexposure, thus showing the protective effect. Conclusion: Thus, our results suggested that RES effectively protected primary lymphocytes from AA-induced genotoxicity probably through reduction of ROS and increased antioxidant function.