This study examined the effects of traditional and nano-scale alcoholic extracts of Portulaca oleracea on liver and kidney function and oxidative stress in male white rats. Forty rats (aged 6–8 weeks, weighing 120–200 g) were used in the animal laboratory of the Department of Biology, Faculty of Education, Al-Qadisiyah University. The animals were randomly divided into five groups (n=8) for a period of 30 days: the control group (tap water), T1 (0.5% hydrogen peroxide), T2 (H₂O₂ + 10 mg/kg alcoholic extract), T3 (H₂O₂ + 10 mg/kg nano-extract), and T4 (H₂O₂ + 5 mg/kg nano-extract). The results showed significant increases (P<0.05) in urea, creatinine, uric acid, ALT, AST, ALP, and markers of oxidative stress, along with a decrease in total antioxidant capacity in the T1 group compared to the control and treatment groups, confirming the presence of hepatic and renal dysfunction resulting from the effect of hydrogen peroxide. The treatment groups (T2–T4) showed significant improvement (P<0.05), with decreased biochemical and oxidative stress markers and increased antioxidant capacity compared to group T1. Group T3 demonstrated higher therapeutic efficacy than groups T2 and T4, while groups T2 and T4 showed similar moderate effects. These results highlight the potential of nanoscale formulations to enhance the bioavailability and therapeutic efficacy of plant extracts in mitigating oxidative damage and restoring organ function under stress-induced conditions in experimental animal models of hydrogen peroxide-induced oxidative stress.