Objectives: Patients with end-stage renal disease (ESRD) are known to experience poorer quality of life (QoL). The present study aimed to evaluate the effects of psychotherapy on QoL among patients with ESRD. Methods: We conducted a systematic search for studies in Medline, PubMed, and SAGE Journals databases from their dates of inception up to 10 April 2020. The inclusion criteria were studies on patients with ESRD, of randomized controlled trial design, published in English language, and with full-text content available online. Two researchers independently extracted articles that met the selection criteria and evaluated the quality of each study. A random-effects meta-analysis was conducted, and data was presented in weighted mean difference (WMD) with a 95% CI. Results: Eight studies were included in the systematic review of which five were entered for meta-analysis. Compared with the control group, the intervention group showed a significant enhancement in QoL, in both physical component summary (PCS) (WMD = 2.52, 95% CI: 0.48–4.57) and mental component summary (MCS) (WMD = 4.22, 95% CI: 1.54–6.89). The heterogeneity across studies for both PCS and MCS was found to be I2 = 0%. Conclusions: The findings indicate that psychotherapy may improve the QoL of patients with ESRD, as compared to the control group. Therefore, psychotherapy can be considered an essential component in the management of ESRD patients for improved psychological and physical outcomes