Background <p>Chronic Kidney disease (CKD) patients face ongoing challenges, including lifestyle changes, medication adherence, and managing treatment complexities and complications daily. In a study, it was found the prevalence of anxiety and depression in CKD patients were 28% and 61.3% respectively. The aim was to find out the impact of nurse-led intervention on the level of anxiety and depression among CKD patients.</p> Methods <p>This study was conducted at Tertiary Care Centre from eastern India and focused on CKD patients. The sample consisted of CKD patients (aged over 18 years) who were proficient in Odia, excluding those with existing mental illness or undergoing psychotherapy. Using block randomization with block sizes of 5 and concealed allocation sequences, participants were allocated to either control or an experimental group.The initial sample size was calculated at 60 participants to accommodate potential dropouts during the study period.</p> Results <p>The nurse-led intervention helped reduce the anxiety levels among CKD patients at different periods, i.e. baseline, 6th week and 12th week of a follow-up visit, which was statistically significant within the group, F(18.594) df-2, <i>p</i> &lt; 0.001 with η²_p(0.243), between the group no statistically significance F(2.27) df-1, <i>p</i> = 0.138 with η²_p(0.38), Interaction effects between the groups across the time point, F(14.007) df-2, <i>p</i> &lt; 0.001 with η²_p(0.07). Nurse-led intervention on depression scores within experimental, between experimental and control groups at different periods, i.e. baseline, 6th week and 12th week of a follow-up visit for CKD patients, which shows a significant effect of time on depression scores (<i>p</i> = 0.05) and a significant overall group difference (<i>p</i> = 0.05). A highly significant time × group interaction (<i>p</i> = 0.001) indicated that depression scores changed differently over time between the experimental and control groups, demonstrating a strong intervention effect.</p> Conclusion <p>The nurse-led intervention significantly reduces the score of hospital anxiety and depression scale in CKD patients, highlighting the vital role of nursing care in improving mental health, sleep quality and overall wellbeing.</p> Trial registration <p>The clinical trial was registered with India’s Clinical Trial Registry (CTRI/2022/08/044974). Registration Date 26-08-22. </p>