Excessive consumption of fructose-rich diets in early life stages increases the risk for developing nephropathy in adulthood. We investigated the potential preventive effects of neonatally administered zingerone on the development of dietary fructose-induced nephropathy. Four-day-old suckling male and female rat pups were orally gavaged (10 ml/kg) with: distilled water (Con group), 20% fructose solution (Fru group), 20% fructose solution + 40 mg/kg zingerone in distilled water (ZFru group), or 40 mg/kg of zingerone (Zgr group) for 14 days. Thereafter, Con and Zgr groups continued on plain drinking water while Fru and ZFru groups drank 20% fructose solution ad libitum for 10 weeks. The Fru group had significantly increased plasma concentration of the renal injury marker kidney injury molecule one (KIM-1) and decreased glomerular urinary space area compared to the controls in both sexes (p < 0.05). These alterations were prevented by neonatally administered zingerone. Zingerone administration neonatally is a potential prophylaxis for longterm high-fructose diet-induced nephropathy.