The toxicological profile of non-nutritive sweeteners like sodium saccharin (Sod.S.) is very much under scrutiny because of their endocrine disrupting role in reproductive health. In this paper, the influence of Sod.S. on the reproductive hormones in both male and female rats was determined, along with their respective modulations by antioxidant vitamins C and E. Eighty adult Wistar rats divided into four groups: control, Sod.S. 5 mg/kg body weight (b.w.), Sod.S. plus vitamin C 150 mg/kg.b.w., and Sod.S. plus vitamin E 100 mg/kg.b.w. was employed. Oral treatment was conducted for 90 days. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were measured. In the male rats, Sod.S. increased E2 by 52%, while significantly suppressing FSH production by 22% compared to controls. Co-administration of vitamin C augmented E2 concentration by 22% compared to Sod.S. group by 58% compared to both control and Sod.S. groups, respectively. Co-administration of vitamin E produced significant increases in FSH concentration by 32% and testosterone by 23% compared to control and Sod.S. groups. In female rats, Sod.S. was increased FSH by 42%, E2 42%, and LH 29%, there was a reduction in the levels of testosterone by 38.52% in comparison to the control. When vitamin C was used with Sod.S., FSH was found to increase by 19%. Conversely, testosterone reduced by 23.39% comparison to the control. In conclusion, Sod.S. altered reproductive hormone profiles in both sexes, indicating endocrine-disrupting potential. Vitamins C and E partially modulated these hormonal disturbances in a sex-dependent manner.