Since oxidative stress has been implicated in most common cause of death, especially in case of cancer and cardiovascular disease, natural substances and spices that show antioxidant effects merit a closer examination. Saffron is the yellow natural spice derived from the flower of Crocus sativus and used as a coloring agent in many foods worldwide. In this study, we determined the total polyphenols content in the Lebanese saffron and the antioxidant effects of different extracts from this saffron in vitro using electrolysis of physiological solution for generation of free radicals (FR) in the presence of colorimetric indicator N,N-di-ethyl-P-phenylenedialanine; the absorbance was measured spectrophotometrically at 515 nm. Histophathological studies allowed us to observe the damages caused by FR in the isolated organs of hamsters (kidney, liver, lungs, and heart) and on the other hand the protection that saffron provided to these vital organs. By using assay kits, we evaluated the levels of lipid peroxidation and superoxide dismutase activity, the important free radical scavenging enzyme. The results showed that both boiled and soaked saffron at 0.45 mg/ml are highly effective against FR generated by electrolysis and against the damages caused to the organs tested as observed by light microscopy. Moreover, saffron significantly (p < 0.05) decreased lipid peroxidation and increased superoxide dismutase activity in all tissues used as compared to control. We concluded that Lebanese saffron strongly protects vital organs against oxidative stress.