Introduction: This study aimed to evaluate how silver nanoparticles, in conjunction with black seed and honey, affected alterations in serum, urine, and renal variables in male mice with renal stones. Methods: Our study considered four target groups: negative and healthy control groups, 125ppm silver nanoparticles treatment, 125mg/kg black seed with 125mg/kg honey, and 125ppm silver nanoparticles treatment. We introduced essential ingredients to the groups from the first to the last day of the experiment, adding 1% ethylene glycol to the drinking water. The researchers investigated serum variables, such as potassium, sodium, calcium, phosphorus, and magnesium, urine factors like citrate, oxalate, and calcium, and tissue factors like kidney weight and crystal count. Results: The results of this paper revealed that the accumulation of calcium oxalate crystals in the treatment group with 125ppm of silver nanoparticles significantly increased compared to other groups (P-value<0. 001). Biochemical examination of urine showed that urine oxalate in the group treated with 125ppm of silver nanoparticles increased by (0. 03±, 0. 78) and in the combined group of honey and black seeds (125mg/kg) and silver nanoparticles (125ppm) increased by (0. 05±, 0. 54). It shows significance (P-value<0. 001). In addition, the results of changes in serum and tissue parameters in both groups showed that they aggravate the formation of kidney stones. Conclusions: According to the findings of this research, silver nanoparticles cause toxicity in serum, urinary, and kidney tissue factors. Therefore, they are not a suitable option for preventing and treating kidney stone patients.