Obesity is a global health concern associated with high morbidity and mortality. Therapeutic strategies include synthetic drugs and surgery, which may entail high costs and serious complications. Orlistat is a pancreatic lipase inhibitor licensed for the treatment of obesity. The current study was carried out to elucidate the modulating effect of Orlistat against obesity-induced kidney toxicity in female rats. A total of 50 female rats were divided into five groups (G1, Control; G2, Orlistat; G3, Obesity; G4, Co- treated Orlistat with Obesity; G5, Post- treated Obesity with Orlistat rat group). The current study revealed that a significant increase in serum urea, creatinine, while a significant decrease in the levels of sodium, potassium, calcium, and chloride ions levels in treated rats with Orlistat while a significant increase in serum urea, creatinine, sodium, potassium, and chloride ions levels in obesity group when compared with a control group. In contrast; a significant decrease in serum urea, Creatinine, sodium, potassium, and chloride ions levels in treated obese rats with Orlistat when compared with the obesity group.  So; Orlistat-induced renal toxicity when used for the treatment of obesity and self-recovered obese rats is safe and better than the use of Orlistat in the treatment of obesity.