Objectives <p>This study examined the effect of mindfulness-based intervention (MBI) on pain and quality of sleep (QoS) in patients with end-stage renal disease (ESRD) undergoing hemodialysis.</p> Method <p>An experimental, repeated measures, parallel control, randomized design was implemented among 60 patients with ESRD (PwESRD) undergoing hemodialysis from April to August 2023 in a hemodialysis unit. Simple random assignment created two equal experimental and control groups (<i>n</i> = 30 each). The experimental group received MBI in addition to hemodialysis, practicing three half-hour sessions per week for 5&#xa0;weeks. Control group patients received hemodialysis treatment as usual, with three hemodialysis sessions for 5&#xa0;weeks without any additional intervention. The study variables (pain and QoS) were measured for both groups at the outset, 2&#xa0;weeks after commencing the intervention, and 5&#xa0;weeks after initiation. Variables were measured by the Numeric Pain Rating Scale (NPRS) and the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Repeated measures analysis of variance (RM-ANOVA) was used to analyze the main study data.</p> Results <p>The mixed-model repeated measures <i>ANOVAs</i> revealed that, compared to the control group, the experimental group showed lower levels of pain (<i>p</i>-value for the group × time interaction &lt; 0.001) and higher levels of QoS (<i>p</i>-value for the group × time interaction &lt; 0.001) over time.</p> Conclusions <p>The encouraging results arising from this research support the deployment of MBI by policymakers as a cost-effective evidence-based practice for patients undergoing hemodialysis, particularly to reduce pain and improve QoS.</p> Preregistration <p>CinicalTrials.gov, Identifier: NCT06064994.</p>