Background and purpose: Patients on hemodialysis experience anxiety and depression. This study aimed to investigate the effect of guided imagery on anxiety, depression, and vital signs in patients on hemodialysis. Materials and methods: This randomized controlled clinical trial was conducted on 80 patients undergoing hemodialysis. The subjects were randomly assigned into two groups: a guided intervention group and a control group. The anxiety and depression were measured using the Hospital Anxiety and Depression Scale. Results: After the intervention, the level of anxiety and depression were significantly lower in the intervention group compared with the control group (p=0.030, p=0.001), respectively. A statistically significant reduction in the respiratory rate and heart rate was reported in the intervention group (p<0.05). Conclusion: Nurses are suggested to use guided imagery along with other interventions for the management of anxiety and depression. It is believed that it can alleviate adverse psychological responses among patients on hemodialysis.