oxic methyl alcohol is widely employed in industry, and it is highly toxic. Only 15 cc ingestion can result in irreversible blindness. The mechanism of toxicity is still a matter of debate. This study was conducted to investigate the incorporation of nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and Nrf2 signaling pathways in the toxicity of the brain, eye, and pancreas following ingestion of methyl alcohol and the possible protective role of PPAR-γ modulators. Twenty-four adult Wister albino rats were divided into four groups of six rats each: a control group, a pioglitazone group, a methanol group, and a combined pioglitazone and methanol group. Oxidative stress markers, random blood sugar, insulin, and pancreatic function measurements were evaluated. Western blot analysis for PPAR-γ and Nrf2 protein expressions was performed. Histopathological examination was performed for eye, brain, and pancreas tissues, and the results were compared. PPAR-γ seemed to be incorporated in the development of organ toxicity associated with methyl alcohol ingestion. The protective role of PPAR-γ modulators was achieved through the improvement of assessed pathways. Therefore, damage can be dramatically improved through incorporating PPAR-γ agonists in the management plan of methyl alcohol toxicity.