Heavy metals are contaminants hazardously affecting the animals’ and humans’ health since they are extensively utilized in the industry where proper physical activity and consuming antioxidant ingredients can be an appropriate solution for decreasing the resultant damages. This work deals with assessing the effects of Crocus sativus L. (saffron) petal extract (SPE) along with eight weeks of interval training on the cytotoxicity of lead (Pb) investigated in exposed adult male mice. SPE reduced the toxic effects of Pb that were indicated by the MTT assay. The morphological alterations of Pb-treated cells were found by fluorescent and normal microscopes when it was co-incubated with SPE. Accordingly, the 50% inhibitory concentration and the 50% lethal dose were calculated. The adult male mice were randomly placed into seven groups (six mice/group) of positive and negative controls, interval training group (Exr), Exr & Pb, SPE, SPE & Pb, and Exr & SPE & Pb treated groups. From the results, SPE did not affect catalase (CAT) activity, but it induced a significant increment of antioxidant enzyme SOD and the levels of malondialdehyde (MDA) is reduced remarkably in the brain. In the last part of the research, mice were exposed to the behavioral tasks examined by step-through ORT, MWM, and YM tests. Having interval training and SPE consumption could reverse the most defective behavioral indicators that may be protecting potential agents inspiringly to the Pb toxicity in the areas with higher heavy metals pollution.