This work was conducted to synthesize whey protein nanoparticles (WPNPs) for the coating of zinc citrate (Zn CITR) at three levels and to study their protective role against CCl4‐induced kidney damage and inflammatory gene expression disorder in rats. Seventy male Sprague‐Dawley rats were divided into seven groups and treated orally for 4 weeks as follows; the control group, the group treated twice a week with CCl4 (5 mL/kg b.w), the groups received CCl4 plus WPNPs (300 mg/kg b.w); the group received 50 mg/kg b.w of Zn CITR or the three formulas of Zn CITR‐WPNPs at low, medium and high doses (LD, MD, and HD). Blood and kidney samples were collected for different assays and histological analyses. The fabricated particles were semispherical, with an average size of 160 ± 2.7, 180 ± 3.1, and 200 ± 2.6 nm and ζ potential of −126, −93, and −84 mV for ZN CITR‐WPNPs (LD), Zn CITR‐WPNPs (MD), and ZN CITR‐WPNPs (HD), respectively. CCl4 significantly increased (p ≤ 0.05) kidney function indices, oxidative stress markers, messenger RNA expression of transforming growth factor‐β1, interleukin (IL)‐1β, IL‐10, IL‐6, inducible nitric oxide synthase, and tumor necrosis factor‐α and significantly decreased (p ≤ 0.05) renal superoxide dismutase, catalase, and glutathione peroxidase along with the histological changes in the kidney tissues. WPNPs, Zn CITR, and Zn CITR loaded WPNPS showed a protective effect against these complications and Zn CITR‐WPNPs (LD) was more effective. WPNPs can be used effectively for coating Zn CITR at a level of 7 mg/g WPNPs to be used as a supplement for the protection of the kidney against different toxicants to enhance immunity and avoid harm of excess Zn.