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Despite being important in the body’s mechanisms, excessive accumulation of manganese (Mn) can induce severe toxicity in vital organs of the body. Thymoquinone (TQ) is extracted from Nigella sativa seeds which recently gained popularity as dietary supplements and plant-based antioxidants. Vildagliptin (VLD) is a dipeptidyl peptidase IV (DPPIV) inhibitor, approved as anti-hyperglycemic agents with cardioprotective and renoprotective effects. The present study aimed to investigate the nephrotoxicity of Mn and the potential protective effects of thymoquinone and vildagliptin. Sixty-four adult male albino rats were equally divided into 8 groups: group I (control, received no medication), group II (vehicle, received normal saline), group III (TQ, 50 mg/kg/day), group IV (VLD, 10 mg/kg/day), group V (MnCl₂, 50 mg/kg/day), group VI (Mn+TQ), group VII (Mn+VLD), and group VIII (Mn+TQ+VLD). Groups VI, VII, and …