Endocrine-disrupting chemicals (EDCs) are a large group of substances able to modulate endocrine-signaling pathways, altering the normal function of the endocrine system. Although the fungicide methyl thiophanate (MT) is not considering a specific reproductive and developmental toxicant, it can induce histopathological damages in rat thyroid and adrenal glands that have a pivotal role in both processes. We investigated the MT effects on adrenal glands of Podarcis sicula lizard, the endemic species of Southern Italy living in open country and in cultivated fields. Reptiles are good bioindicators because they are easily harvested; they have a wide distribution and large populations. Moreover, they have good sensitivity to contaminants, and bioaccumulate and biomagnify pollutants to levels equal to or greater than those of birds and mammals. We used 1.5% MT/water to pollute terraria, food, and water twice a week for 15 and 30 days, and we evaluated adrenal toxicity through biochemical (adrenal and pituitary hormone plasma levels) and histological parameters (adrenal gland histopathology). We demonstrated a time-dependent increase of corticosterone plasma levels and a decrease of ACTH plasma levels, a hypertrophy of the steroidogenic tissue, and an enlargement of blood capillaries. Moreover, we observed a time-dependent increase of adrenaline plasma levels and adrenaline-producing cells, and an opposite trend of noradrenaline plasma concentrations. We also observed lymphocyte and macrophage infiltrations, signs of cell degeneration. Our findings on the bioindicator P. sicula provide an interesting basis to further elucidate the systemic mechanisms of EDCs.