Microplastics, such as polystyrene microplastics (PS-MPs), have become an emerging environmental hazard for animals and humans. Long-term exposure to PS-MPs has led to neurotoxicity, reproductive dysfunction, and carcinogenesis. The goal of this study was to evaluate the effect of sub-chronic exposure of PS-MPs on metabolic and reproductive functions in female rats. The PS-MPs were prepared by cryogenic technique. The PS-MPs were given orally to female Wistar rats for 45 days at 2.5, 5, and 10 mg/kg/day. The average PS-MPs' size diameter was 876 nm. The PS-MPs administration resulted in a significant decrease in the activity of superoxide dismutase and catalase in the liver and ovary. The effect of PS-MPs on reduced glutathione and lipid peroxidation in the liver and ovarian tissues of rats was statistically insignificant. The PS-MP exposure exhibited an increase in the levels of triglycerides, total cholesterol, and low-density lipoprotein and decrease in high-density lipoprotein. The PS-MPs caused glucose intolerance and increase in insulin. Moreover, the PS-MP exposure increased follicle stimulating hormone, estradiol, and testosterone. Serum level of interleukin-6 and nuclear factor kappa B (NF-κB) was elevated in animals treated with PS-MPs. The PS-MP exposed rats showed normal ovarian histology, but activated hepatic stellate cells and liver fibrosis. It is concluded that the sub-chronic exposure to PS-MPs resulted in metabolic and endocrine disruption in female rats through oxidative damage, hormonal imbalance, and chronic inflammation.