Objective: Given the significant impact epilepsy can have on the Health Related Quality of Life (HRQoL) of individuals with this condition and their families, there is great clinical interest in evidence-based psychological treatments aimed at enhancing well-being in people with epilepsy (PWE). An evaluation of the current evidence is needed to assess the effects of psychological treatments for PWE on HRQoL outcomes in order to inform future therapeutic recommendations and research designs.Methods: The operational definition of 'psychological treatments' included a broad range of interventions that use psychological or behavioral techniques designed to improve HRQoL, psychiatric comorbidities, and seizure frequency and severity for adults and children with epilepsy. A systematic literature search was conducted in line with Cochrane criteria for randomized controlled trials (RCTs) and quasi-RCTs investigating psychological treatments using HRQoL outcome measures as primary or secondary outcome measures. Standard methodological procedures required by the Cochrane Collaboration were used for data collection and analysis. Results: Twenty-four completed RCTs were included in this review (2,439 participants). Based on satisfactory methodological homogeneity, data from nine studies (468 participants) providing Quality of Life in Epilepsy-31 (QOLIE-31) outcomes were pooled for meta-analyses showing significant mean changes for QOLIE-31 Total Score and six subscales. The significant mean changes of QOLIE-31 Total Score [mean improvement of 5.68 points (95% CI 3.11 to 8.24, p < 0.0001)] and three subscales (Emotional Well-being, Energy/Fatigue, Overall QoL) exceeded the threshold of Minimally Important Change (MIC), indicating a clinically meaningful post-intervention improvement of QoL. Overall, the meta-analysis quality of evidence was characterized as “moderate” due to risk of bias present in eight of the nine included studies 1, 2. A narrative synthesis was conducted for all trials and outcomes that were not entered in the meta-analysis.Significance: These results provide moderate quality evidence that psychological treatments for adults with epilepsy may enhance HRQoL in people with epilepsy.