Background: Alzheimer's caregivers frequently report experiencing high levels of stress. Objectives: This research aimed to investigate the effectiveness of Acceptance and Commitment Therapy (ACT) on caregiver burden and psychological flexibility in caregivers of aged patients with Alzheimer's disease. Materials and Methods: This pretest-posttest design with a three-month follow-up was performed on caregivers of aged Alzheimer's patients who visited the neurology clinic in the spring of 2023. Following the administration of the Acceptance and Action Questionnaire-II and the Caregiver Burden Inventory in the pre-test, a sample of 30 individuals was randomly assigned to the experimental and control groups. The ACT intervention was implemented for the experimental group over eight sessions, each lasting 90 minutes. Upon completion of the intervention, participants were re-evaluated in the posttest and follow-up. Data were analyzed using chi-square, repeated measures analysis of variance, and Bonferroni's post hoc test at a significance level of 0.05. Results: There between-group comparison showed a significant difference between intervention and control group indicating improvement of all study variables in the intervention compared to the control group. The highest difference was observed for psychological flexibility (27.281, 95%CI: 24.977, 29.586) followed by caregiving burden (17.87, 95%CI: 15.685, 20.00) from baseline to follow-up. Conclusion: ACT effectively reduced caregiver burden and enhanced psychological flexibility in caregivers of aged patients with Alzheimer's disease. Clinical psychologists and health professionals are advised to provide better support for caregivers in their roles and promote their mental well-being through intervention programs. By improving their mental health, they can be more effective in assisting with the treatment process of aged patients with Alzheimer's disease.