Cognitive symptoms are prevalent across neuropsychiatric disorders, increase distress and impair quality of life. Self-guided digital interventions offer accessibility, scalability, and may overcome the research-to-practice treatment gap. Seventy-six trials with 5214 participants were identified. A random-effects meta-analysis investigated the effects of all digital self-guided interventions, compared to controls, at post-treatment. We found a small-to-moderate positive pooled effect on cognition (k = 71; g = −0.51, 95%CI −0.64 to −0.37; p < 0.00001) and mental health (k = 30; g = −0.41, 95%CI −0.60 to −0.22; p < 0.0001). Positive treatment effects on fatigue (k = 8; g = −0.27, 95%CI −0.53 to −0.02; p = 0.03) and quality of life (k = 22; g = −0.17, 95%CI −0.34 to −0.00; p = 0.04) were only marginally significant. No significant benefit was found for performance on activities of daily living. Results were independent of control groups, treatment duration, risk of bias and delivery format. Self-guided digital transdiagnostic interventions may benefit at least a subset of patients in the short run, yet their impact on non-cognitive outcomes remains uncertain.