© 2022 S. Karger AG, Basel. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Introduction: In this study, it was aimed to investigate the effect of thymoquinone (TQ) on oxidative stress and apolipoprotein E (ApoE) in an experimental Alzheimer's model created with AlCl3 and D-galactose in rats. Methods: Thirty-six Wistar Albino male rats saline group (Group 1), aluminum chloride (AlCl3) + D-galactose (D-Gal) group (Group 2), AlCl3 + D-Gal + TQ group (Group 3) were divided into 3 groups. The study was completed with 33 rats. Group 1 was given saline intraperitoneally (i.p) for 28 days. 2nd group; D-Gal at a dose of 60 mg/kg/day and AlCl3 at a dose of 40 mg/kg/day were given i.p. daily for 28 days. 3rd group; D-Gal at a dose of 60 mg/kg/day and AlCl3 at a dose of 40 mg/kg/day were given i.p. daily for 28 days. Group 3 rats were given 20 mg/kg/day TQ in corn oil by gavage for 14 days. Malonyl dialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAS), total oxidant capacity (TOS), glutathione peroxidase (GsH-Px), and ApoE levels were determined in the blood and brain tissues of rats in all three groups. One-way ANOVA test was used in the statistical analysis of the data. Results: Means of TAS, TOS, GSH-Px, SOD, MDA, and ApoE in blood and brain tissue of all three groups (excluding ApoE in brain tissue) were different from each other and this difference was statistically significant (p < 0.05). Conclusion: In this study, TQ, it was determined that all oxidative stress parameters examined had positively affected and decreased blood tissue ApoE levels. TQ can be used as an antioxidant and curative in Alzheimer's disease.