<b><i>Background and Aim:</i></b> Alzheimer disease (AD) is the most common cause of dementia. Currently, there is no disease-modifying therapy for AD. We aimed to evaluate the long-term efficacy and safety of MLC601 in the treatment of AD. <b><i>Methods:</i></b> In this open-label extension study, patients with mild to moderate AD according to DSM-IV criteria were recruited. Patients received MLC601 capsules 3 times a day for 4 years. Cognitive function was assessed every 6 months using Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores. Safety profiles, including adverse events (AEs), and treatment-related abnormality in laboratory tests were also reported. <b><i>Results:</i></b> Of a total of 122 patients, 105 completed the study. The mean age was 66.8 ± 6.3 years at the beginning of the study. Sixty-five (61.9%) were female. The mean (±SD) change in MMSE and ADAS-Cog scores at the end of the study was 2.1 (±3.8) and –5.1 (±8.7), respectively. Repeated measure analysis revealed a statistically significant change in both scores (<i>p</i> &#x3c; 0.001). No patient left the study due to an AE. No abnormality was noted in lab tests. Gastrointestinal symptoms were the most commonly reported AEs. <b><i>Conclusion:</i></b> The efficacy of treating AD patients with MLC601 over 4 years has been demonstrated in the present study. Overall, it seems that the safety and efficacy of MLC601 is promising compared to currently prescribed treatments.