Cisplatin is among the most frequently utilized drugs for addressing malignant tumors, yet it can lead to organ harm, especially hepatotoxicity and nephrotoxicity. Furthermore, the anticoagulant rivaroxaban could poten­ tially cause injury to the liver and kidneys. This research aimed to examine the protective benefits of nebivolol, known for its pleiotropic and tissue-protective characteristics, against the harmful effects of rivaroxaban and cisplatin on the liver and kidneys. Male rats received cisplatin and/or rivaroxaban, and we evaluated hepato­ toxicity and nephrotoxicity by measuring serum concentrations of AST, ALT, LDH, albumin, bilirubin, creatinine, and blood urea. We also measured MDA, GSH, GPx, NO, TNF-α, and IL-6 in kidney and liver homogenates. Histopathological analysis was performed on liver and kidney tissue sections, and immunohistochemical detection of caspase 3 in liver tissue and NF-κB in kidney tissue was conducted. Our findings demonstrated that nebivolol supported the preservation of the liver and kidney structure and function by reducing the biochemical and pathological alterations caused by cisplatin and rivaroxaban. Nebivolol decreased the elevations in MDA, TNF-α, and IL-6 levels while maintaining GSH, GPx, and NO levels in liver and kidney tissues. Moreover, nebivolol lowered the levels of caspase-3 in the liver and NF-κB in the kidneys. In conclusion, our study indicates that nebivolol protects the liver and kidneys from the detrimental effects of cisplatin and rivaroxaban.