This study aimed to investigate the effects of orally administered Titanium dioxide (TiO₂) nanoparticles on reproductive health in rats. A total of 20 rats, aged 2 to 3 months, were divided into two groups. One group (n=10) received a dosage of 250mg/kg bw TiO₂ (15 nm particle size) daily for 28 days, while the other group (n=10) received only tap water as a control. At the end of the study, rats were euthanized, epididymal sperm samples were collected and testicular tissues were examined using both hematoxylin-eosin (H&E) staining and immunohistochemical techniques to assess the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and hypoxia-inducible factor 1α (HIF-1α). Oxidative stress levels were measured by Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Malondialdehyde (MDA) levels, and Glutathione peroxidase (GSH-Px) activity. The results indicated that the oral administration of TiO₂ nanoparticles significantly impaired sperm quality parameters (P<0.01). In the TiO₂-treated group, seminiferous tubule diameter and epithelial height were lower compared to control group (P<0.05). Furthermore, the levels of 8-OHdG, indicating DNA damage, and HIF-1α, a marker of tissue hypoxia, were increased in the testicular tissue. Additionally, the levels of oxidants (TOS and MDA) were increased, while antioxidant markers (TAS and GSH-Px) were decreased in TiO₂-treated group. In conclusion, oral administration of TiO₂ nanoparticles induces DNA damage, adversely affects epididymal semen quality, and elevates oxidant levels in testicular tissue. These results underscore the detrimental effects of TiO₂ nanoparticles (<100nm, especially <25nm) on reproductive health and highlight the importance of further investigation into their potential adverse effects in humans.