Substance use disorder (SUD) is on the rise globally, and nurses are not prepared to care for this population. The purpose was to determine if a 4-hour antistigma intervention improved prelicensure student nurse attitudes and perceived stigma toward people with SUD. This was a nonrandomized quasi-experimental survey study. Participants completed the 20-item Drug and Drug Problems Perception Questionnaire (DDPPQ), the 8-item Perceived Stigma of Substance Abuse Scale (PSAS), and the 13-item Marlowe-Crowne Social Desirability Scale at baseline and repeated the DDPPQ and PSAS postintervention. Paired t tests were used to determine the mean differences in the total DDPPQ and total PSAS scores. After the antistigma intervention, there was a significant improvement in overall therapeutic attitudes (t = 8.4, df = 108, P < .001) and perceived stigma (t = -2.5, df = 108, P = .01) in undergraduate nursing students (n = 126). Incorporating antistigma educational approaches may lead to more involvement and compassionate care for people with SUD.