The aim of this study was to investigate the potential neuroprotective efficacy of coenzyme Q10 (CoQ10) against doxorubicin (DOX) -induced behavioral disturbances in rats. Female rats were randomly assigned into 4 groups as control, CoQ10, DOX, and DOX plus CoQ10. The CoQ10 groups received CoQ10 (200 mg kg−1) for 21 days, and the DOX groups received DOX (4 mg kg−1) on days 7 and 14 of the study. The open field (OF) and elevated plus maze (EPM) tests were performed to assess locomotor activity and anxiety levels. Additionally, malondialdehyde (MDA), and protein carbonyl (PC) levels and acetylcholinesterase (AChE), and glutathione peroxidase (GPx) activities and total antioxidant capacity (TAC) were quantified in brain tissue. DOX administration caused alterations in locomotor activity, and anxiety-like behaviors. Moreover, DOX produced significant elevation in AChE activity. PC level and GPx activity tended to alter with DOX administration. Co-treatment with CoQ10 significantly attenuated DOX-induced behavioral alterations via improving AChE activity in the brain tissue of rats. CoQ10 treatment may be potential for the alleviation of DOX-induced behavioral disturbances. This improvement might be due to the inhibition of AChE activity.