Background: There are gender differences in the oxidation-reduction reactions. Doxorubicin (Dox) is a chemotherapeutic drug that can produce oxidative stress which may require prevention by antioxidants. Aim: The study aimed to investigate the gender-dependent changes in Dox-induced oxidative stress, and the protective effects of coenzyme Q10 (CoQ10). Materials and Methods: Rats were administered CoQ10 orally for 17 days. On day 13, some rats receiving CoQ10 received a single intraperitoneal dosage of Dox, whereas other rats received normal saline. Glutathione (GSH), malondialdehyde (MDA), and total anti-oxidant capacity (T-AOC) were measured in both genders of albino rats. Results: Dox significantly reduced both GSH and T-AOC levels and caused a significant increase in MDA. The administration of CoQ10 significantly prevented these changes. Dox caused a larger reduction in GSH in males than in females, while CoQ10 caused more protection in females. Dox caused a higher increase in MDA levels in males. Conclusion: Pre-treatments with CoQ10 may protect against Dox-induced oxidative stress, with gender-dependent variations in the extent of these Dox/CoQ10 effects.