Background <p>Hemodialysis patients suffer from physical and mental symptoms for which aromatherapy might be useful. This study aimed to determine the effectiveness of Melissa officinalis L. (Lemon Balm) essential oil inhalation on anxiety and the burden of symptoms in hemodialysis patients.</p> Methods <p>This study is a randomized clinical trial with a pretest-posttest design. Sixty-eight hemodialysis patients were randomly divided into intervention (who underwent Melissa officinalis L. inhalation aromatherapy 3 times a week for one month) and control (who inhaled refined sweet almond oil) groups. The intervention in both groups was conducted during the hemodialysis session. The data were collected using the state-trait anxiety inventory and Dialysis Symptom Index. Data were analyzed through SPSS-25, using Mann-Whitney, Wilcoxon, t-tests and MANOVA.</p> Results <p>Before the intervention, both groups were similar in terms of anxiety and symptoms burden (<i>P</i> &gt; 0.05). However, after the intervention, a significant difference was found between the groups in terms of state and trait anxiety, and severity of constipation, nausea, vomit, diarrhea, swelling in legs, muscle cramps and shortness, worry, nervousness and anxiety, and trouble staying asleep. Moreover, after the intervention, a significant difference was observed between the groups regarding the prevalence of symptoms burden such as feeling anxious and having a dry mouth (<i>P</i> &lt; 0.05).</p> Conclusion <p>Melissa officinalis L. essential oil inhalation aromatherapy reduced the symptoms burden and anxiety in hemodialysis patients. Given the effectiveness of aromatherapy in hemodialysis patients, it is suggested that healthcare workers should use this complementary and integrative health to reduce the anxiety and symptoms burden in hemodialysis patients.</p> Trial registration RCT registry <p>Iranian Registry of Clinical Trials (IRCT) number: IRCT20191021045178N3; Registration date 27/04/2021.</p>