Background <p>Patients with diabetes and hypertension require long-term medication, which may increase the chance of non-adherence to medications. Medication therapy management has been shown to positively impact medication adherence. This study aimed to assess the impact of medication therapy management on medication adherence among patients comorbid with diabetes mellitus and hypertension.</p> Methods <p>A cluster randomized controlled trial was conducted at outpatient clinics from January 03 to July 18, 2022. The hospital was randomly assigned to either the intervention or control group. The patients attending hospitals assigned to the interventional group received medication therapy management services in addition to usual care. A systematic random sampling technique was used to select the study participants from each hospital. Medication adherence was assessed using the Adherence in Chronic Diseases Scale. SPSS version 24.0 was used for data analysis. The independent sample t-test and chi-square test were used to compare the variables.</p> Result <p>Of 402 eligible patients, 201 were randomly assigned to the medication therapy management intervention group and 201 patients were randomized to the control group. No significant differences were observed in the baseline characteristics of the patients. The adherence rate in the intervention group increased by 50%, whereas it remained fairly constant in the control group, and the difference was statistically significant (<i>p</i> &lt; 0.001).</p> Conclusion <p>The current study showed that medication therapy management intervention improved the patients’ medication adherence. Hospitals should strengthen and integrate clinical pharmacy services into their healthcare system.</p> Trial registration <p>ClinicalTrials.Gov NCT06112925.</p>