Rising rates of mental health problems in undergraduate students is a critical public health issue. There is evidence supporting the efficacy of acceptance and commitment therapy (ACT) in decreasing psychological symptoms in undergraduates, which is thought to be facilitated through increases in psychological flexibility (PF) and decreases in psychological inflexibility (PIF). However, little is known about the effect of ACT on these processes in undergraduates. We conducted a systematic review and three-level meta-analysis examining this effect in 20 studies, which provided 56 effect sizes. A combined sample of 1,750 undergraduates yielded a small-to-medium overall effect ( g = .38, SE = .09, p < .001, 95% CI: [0.20, 0.56]). This effect did not depend on control group type, intervention modality, number of sessions, the questionnaire used, whether PF or PIF was measured, or participant age. However, there was a significant mean effect only in studies with a specific clinical target, but not in those without one. Furthermore, the higher the percentage of female participants, the lower the reported effect size. Results suggested that ACT may increase PF and decrease PIF in undergraduates and highlighted various conceptual and measurement issues. Study protocol and materials were preregistered (https://osf.io/un6ce/).