Kidney stones, also known as calcium oxalate (CaOx) nephrolithiasis, are often asymptomatic, leading to kidney injury and renal failure complications. Corilagin is a gallotannin found in various plants and is known to elicit various biological activities. The present study aimed to elucidate the renoprotective effect of corilagin against the rats’ renal stones deposition. The rats were induced for nephrolithiasis (CaOx deposition) using 0.75% ethylene glycol in their drinking water. Then, they were treated with corilagin at 50 and 100 mg/kg/day for 4 weeks. At the end of the experimental period, the rats were killed; blood and renal tissues were collected for various histological, biochemical, and gene expression analyses. The results demonstrated that the rats had renal calculi displaying a significant increase in serum creatinine (59.39 μmol/L) and blood urea nitrogen (19.03 mmol/L) levels compared with controls. Moreover, the malondialdehyde (13.29 nmol/mg) level was found to increase with a profound reduction in antioxidants’ activities with upregulated inflammatory cytokines. In contrast, the RT‐PCR and immunohistochemistry analysis demonstrated a substantial reduction in cell survival markers PPAR‐γ and PI3K/Akt with an apparent increase in apoptosis markers genes expressions in rats suffering from renal stones. Thus, the present study results suggest that corilagin could suppress renal CaOx crystal‐induced oxidative stress, inflammatory response, and apoptosis via PPAR‐γ and PI3K/Akt‐mediated pathway.