Background: Natural compounds exhibit nephroprotective effects by enhancing antioxidant defenses, reducing cellular damage, and improving renal filtration. Objective: This study evaluated the combined protective effects of Gum Arabic and vitamin C against glycerol- induced nephrotoxicity in rats. Methods: Fifty male rats were assigned to five groups: control, glycerol-induced nephrotoxicity, gum Arabic + glycerol, gum Arabic + vitamin C + glycerol, and gum Arabic alone. Kidney and liver function markers (urea, creatinine, uric acid, liver enzymes, LDH, CK, glucose, CRP), oxidative stress markers (MDA, NO, GSH, GPx, GST, GR, TAC), hematological parameters, histopathology, immunohistochemistry (caspase-3, PCNA), and gene expression of kidney injury and inflammatory markers (KIM-1, NGAL, TNF α , IL-1β, MCP-1, COX-2) were assessed. Results: Glycerol intoxication impaired renal function, induced hepatic dysfunction, increased oxidative stress, and caused hematological alterations and electrolyte imbalances. Treatment with Gum Arabic and vitamin C improved renal and liver function, reduced oxidative stress, modulated inflammatory markers, and restored hematological balance. Gene expression analysis confirmed the downregulation of inflammatory and kidney damage markers. Conclusion: Nutraceuticals may offer a safe, cost-effective, and complementary approach to mitigating kidney damage. Gum Arabic and vitamin C demonstrated nephroprotective, hepatoprotective, and antioxidant effects, supporting their potential as a natural therapeutic strategy against nephrotoxicity.