Introduction: With widespread applications of nanoparticles (NPs) including titanium dioxide nanoparticles (TiO2NPs) in different fields, many adverse effects may threaten both environmental and medical health including the male reproductive system. Aim of this work: To examine the ameliorative effect of N-acetyl cysteine (NAC) and curcumin (Cur) against TiO2NPs induced testis toxicity in adult albino rats. Materials and Methods: Sixty-four adult male albino rats were classified into eight groups. Group 1: control received a regular diet, water, and normal saline. Group 2: vehicle, received corn oil. Group 3: gavaged orally with NAC (100 mg/kg). Group 4: orally gavaged with curcumin (200 mg/kg) once a day. Group 5: gavaged orally with TiO2NPs (100mg/kg) once a day. Group 6: orally gavaged once daily with TiO2NPs (100 mg/kg) and NAC (100 mg/kg). Group 7: orally received TiO2NPs (100mg/kg) and curcumin (200mg/kg) once a day. Group 8: gavaged orally TiO2NPs (100mg/kg) followed by NAC (100mg/kg) and curcumin (200mg/kg). Results: The results revealed that TiO2NPs induced a significant decrease in final body weight, weight body gain, and testis weight testicular tissues, TiO2NPs increased oxidative stress as evidenced by decreased levels of antioxidants such as superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) and higher levels of the lipid peroxidation marker malondialdehyde (MDA). In addition to harming the testicular histological architecture, TiO2NPs significantly decreased the levels of the sex hormones testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). They also significantly decreased sperm motility, viability, cell count, and concentration. In the testicular tissues, TiO2NPs led to the downregulation of 17-beta hydroxysteroid dehydrogenase 3 (17-HSD) and the overexpression of proapoptotic gene (Bax) transcripts. Conversely, NAC and/or curcumin had a protective effect on testicular tissue. Conclusion: We propose that NAC and curcumin may be employed to lessen the toxicity and oxidative damage caused by ingesting TiO2NPs. TiO2NP exposure caused oxidative damage and morphological injury in the testis.