Background: Mancozeb is a powerful fungicide used to combat fungal infections in crops. However, population-based studies proved its use has resulted in environmental and human health hazards. Aim of the work: to evaluate the effect of mancozeb on the thyroid gland histological structure and function of adult male albino rats and the role of concomitant pomegranate fruit extract supplementation. Materials and methods: Twenty-nine male adult albino rats were classified into three groups: Control, mancozeb-treated (700 mg/Kg), and mancozeb with pomegranate fruit extract (700 mg/Kg body weight mancozeb and PFE 150 mg/kg/day) groups. After 4 weeks, blood samples were collected to estimate T4, T3, and TSH. Tissue superoxide dismutase (SOD), malondialdehyde (MDA) and plasma-reduced glutathione (GSH) were estimated. Total miRNA extraction and reverse transcription to cDNA and quantitative real-time PCR for specific miRNAs were assessed. Thyroid gland specimens were processed for histological and immunohistochemical examination then morphometric and statistical analyses were done. Results: In the mancozeb-treated group many small follicles with reduced colloid content, vacuolated follicular cells with irregular shrunken nuclei, dilated RER, and atrophied apical microvilli were observed. PCNA immune reaction and the oxidative stress markers were highly elevated in group II; while in group III, it was close to the control group. Conclusion: Concomitant supply of pomegranate fruit extract with mancozeb intake has proved a potential efficacy to protect the rat's thyroid gland histological structure and biochemical parameters. Hence, we advise more studies in this field and apply strict precautions for the workers and the mancozeb-exposed people.