This study examined the possible defensive role of coenzyme Q10 (CQ10) against the impact of cadmium (Cd) and titanium dioxide nanoparticle (TNP) exposure on rat kidneys. Distilled water (1 mL/rat), corn oil (1 mL/rat), 10 mg CQ10/kg b.wt, 50 mg TNP/kg b.wt, 5 mg Cd/kg b.wt, TNP + Cd, or TNP + Cd + CQ10 was administered orally to seven groups of 70 male Sprague Dawley rats for 60 days. The findings demonstrated that TNP and/or Cd exposure considerably raised serum levels of several renal damage products, disturbed electrolyte balance including sodium, potassium, and calcium, decreased antioxidant enzyme concentration in the kidneys, and elevated malondialdehyde. In addition, rats exposed to TNP and/or Cd had significantly higher levels of renal titanium and Cd. In addition, rats exposed to TNP and/or Cd showed significant histopathological lesions and collagen deposition as revealed by H and E and Masson trichrome staining, respectively. The kidneys were severely damaged by the combined effects of TNP and Cd, although CQ10 greatly mitigated these effects. According to the study, exposure to TNP and Cd can damage the kidneys’ function and structure, especially when combined. However, CQ10 can protect against TNP and Cd’s nephrotoxic effects.