We examined the efficacy of cognitive and behavioral interventions for improving symptoms of depression and anxiety in adults with neurological disorders. A pre-registered systematic search of Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, Embase, and Neurobite was performed from inception to May 2024. Randomized controlled trials (RCTs) which examined the efficacy of cognitive and behavioral interventions in treating depression and/or anxiety among adults with neurological disorders were included. Estimates were pooled using a random-effects meta-analysis. Subgroup analyses and meta-regression were performed on categorical and continuous moderators, respectively. Main outcomes were pre- and post-intervention depression and anxiety symptom scores, as reported using standardized measures. Fifty-four RCTs involving 5372 participants with 11 neurological disorders (including multiple sclerosis, epilepsy, stroke) were included. The overall effect of interventions yielded significant improvements in both depression (57 arms, Hedges' g = 0.45, 95% confidence interval [CI] 0.35–0.54) and anxiety symptoms (29 arms, g = 0.38, 95% CI 0.29–0.48), compared to controls. Efficacy was greater in studies which employed a minimum baseline symptom severity inclusion criterion for both outcomes, and greater in trials using inactive controls for depression only. There was also evidence of differential efficacy of interventions across the neurological disorder types and the outcome measure used. Risk of bias, intervention delivery mode, intervention tailoring for neurological disorders, sample size, and study year did not moderate effects. Cognitive and behavioral interventions yield small-to-moderate improvements in symptoms of both depression and anxiety in adults with a range of neurological disorders.