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Introduction: Recent studies highlighted the role of olive polyphenols in disrupting the ordered structure of highly cytotoxic amyloid beta protofibrils and the efficacy of a derivatized form of glutathione to counteract neuronal oxidative stress affecting specific brain regions at early stages of Alzheimer's disease (AD) pathogenesis. We performed a randomized cross-over clinical trial to evaluate their potential benefits in mild AD., Methods: Oleuropein and S-acetyl glutathione were administered as dietary supplement for 6 months to 18 patients diagnosed for probable mild AD according to International Working Group 2 criteria. Patients underwent an extensive cognitive and behavioral neuropsychological test battery at the beginning and end of the study to evaluate cognitive deterioration, memory, visuospatial abilities, attention, language, executive functions, and behavioral disorders. We compared patients receiving treatment to patients receiving no treatment., Results: All the measured neurocognitive parameters stabilized or improved after the treatment in all patients., Discussion: Dietary supplement with olive polyphenols and bioavailable glutathione could be useful for patients diagnosed with mild AD., Competing Interests: Massimo Marianetti, Silvia Pinna, Angelo Venuti, and Gianfranco Liguri did not receive support for the submitted work nor receive any support outside the submitted work in the past 36 months. Massimo Marianetti, Silvia Pinna, and Angelo Venuti do not have any relationships/activities/interests to disclose. Gianfranco Liguri has been in the past 36 months a shareholder and unpaid scientific advisor for Innbiotec Pharma Srl, which developed the nutraceutical formulation and he has no other relationships/activities/interests to disclose. All the authors have nothing else to disclose according to the ICMJE Disclosure Form., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)