Recently, a few different vaccines have been developed to help end the COVID-19 pandemic. These vaccines have made significant progress toward controlling the disease. Multiple factors contribute to the immunity level that these vaccines can stimulate, including sex. The effect of gender on other vaccines’ efficacy has been studied before. The results of these studies are mentioned below. Genetic and hormonal differences between men and women are among the mechanisms suggested for the difference in vaccine efficacy in men and women. Sex hormones play various roles in stimulating or suppressing the immune system. As a result, they are responsible for the intensity and speed at which the vaccine establishes the immune response. In this narrative review study, we discuss the differences in COVID-19 vaccine efficacy and safety between the two genders and the reasons for these differences.