Background <p>Herpes simplex virus type 2 (HSV-2) infection is a prevalent lifelong infection and the leading cause of genital ulcer disease (GUD), yet no vaccines or curative interventions are currently available. Emerging curative approaches have demonstrated proof-of-concept efficacy in preclinical studies, but their potential population-level impact remains unknown. This study assessed the potential impact of curative therapy on HSV-2 disease burden and transmission.</p> Methods <p>A dynamic HSV-2 transmission model was developed for the United States and calibrated to prevalence estimates from the National Health and Nutrition Examination Surveys. Curative therapy was assumed to be introduced in 2030 and scaled to 20%, 50%, or 80% coverage by 2040 under two scenarios: (i) treatment of symptomatic individuals only and (ii) treatment of all individuals with HSV-2 infection.</p> Results <p>Here we show that, by 2050, at 80% coverage, curative therapy for symptomatic individuals reduces the number of 15–49-year-olds with GUD and GUD days by 86.7% and 86.2%, respectively, and decreases the incidence rate and annual new infections by 54.0% and 51.7%, averting 5.4 million cumulative infections. The numbers needed to treat to avert one prevalent or incident symptomatic HSV-2 infection, one incident HSV-2 infection, and one year of GUD days are 0.90, 3.4, and 0.61, respectively.</p> Conclusions <p>Curative therapy could substantially reduce HSV-2 incidence and recurrent GUD, yielding population-level benefits beyond individual cure.</p>