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Background: Natural products from various sources tend to be potential candidates for drug discovery; zeolite has valuable biopharmaceutical efficiencies because of its physical and chemical properties. The current study aimed to investigate the antidiabetic and preventive effect of both natural zeolite (NZ) and synthetic zeolite (SZ) against induced diabetes and its complication. Methods: Adult male rats were arranged in six groups: 1) normal control, 2) NZ-ingested (300 mg/kg/day), 3) SZ-ingested (300 mg/kg/day), 4) untreated induced-diabetics, 5) induced-diabetics treated with NZ (300 mg/kg/day), and 6) induced-diabetics treated with SZ (300 mg/kg/day). Results: Post treatment of induced-diabetic animals, the results declared that both NZ and SZ exhibited a remarkable drop in glucose, HbA1c, TNF-α and IL1β levels associated with a significant raise in insulin and CD4 + values towards the corresponding values of the control group. The histological findings performed a notable restoration of the islets’ architecture and size and ameliorated karyolysis. Also, immunohistochemical results showed a marked improvement in insulin immunoreactivity confirming the biochemical findings. Conclusion: These results concluded that both NZ and SZ zeolite exhibited preventive and anti-diabetic potential; this effect could be due to the amphoteric character preventive absorption of sugar, preventing beta cell and modify the disorders in the redox state.