Iron oxide nanoparticles (IO-NPs) are involved in many medical fields, besides these nanoparticles can cause cytotoxicity and oxidative stress so it is requisite to estimate the safety of NPs in vivo. Purpose of the present experiment is to investigation the beneficial action of Aloe vera (AV) in reducing oxidative stress caused by exposure to IO-NPs in an animal model. Twenty-four rats were used and divided into three equal groups. Rats that were without any doses were included in the CON group, while IO-NPs rats were administered orally iron oxide nanoparticles, and IO-NPs + AV rats were co-administered of Aloe vera with iron oxide nanoparticles. The experiment was continued for 14 uninterrupted days, after which animals were sacrificed and the serum was obtained for oxidative stress analyzes. The results showed a significantly higher MDA accompanied by lower levels of GSH and CAT for rats receiving IO-NPs when they were compared to control group, but the combined dose with AV significantly improved those toxic changes. We concluded that AV extract can reduce intoxication of IO-NPs on serum oxidative stress indicators.