Background: Doxorubicin (DOX) is a potent chemotherapy agent; however, its use may lead to cardiac, hepatic, and renal dysfunction. Kleinhovia hospita L extract contains antioxidant compounds that have been shown to reduce chemical-induced hepatotoxicity., Objectives: This study aimed to examine the protective effects of Kleinhovia sp. extract to reduce DOX acute toxicities., Materials and Methods: Thirty male rats were assigned to the following groups: Group I as controls, Group II was given DOX i.p. injection (25 mg/kg); Groups III, IV, and V were treated with Kleinhovia sp. extract 100, 250, and 500 mg/kg orally for 5 days, respectively, prior to DOX i.p. injection. After 24 h, blood and organs were analyzed for biomarker levels and histopathological changes., Results: DOX treatment in Group II significantly increased creatine kinase-MB (CK-MB), aspartate transaminase (AST), alanine transaminase (ALT), and urea levels compared to controls. Kleinhovia sp. extract at any given dose significantly improved ALT and AST; yet, CK-MB levels only reduced with 250 mg/kg dose (Group IV). Urea and creatinine levels in Kleinhovia sp. groups were also lower compared to DOX-treated rats, but it was not significant. Histopathological analysis showed improved liver, heart, and renal tissue structures in Kleinhovia sp-treated rats, especially at higher doses., Conclusion: Kleinhovia sp. extract at any dose given protected the rats from liver toxicity, but only at dose 250 mg/kg reduced cardiac toxicity. Although renal biomarkers were insignificantly lower, renal architecture was improved with Kleinhovia sp. treatment., Summary: Doxorubicin (25 mg/kg) i.p injection led to elevated ALT, AST, CK-MB and urea levels in rats.At the given dose, doxorubicin induced pathological changes in cardiac, liver and renal tissues.Pretreatment with Kleinhovia sp. extract prior to doxorubicin injection significantly reduced the elevation of ALT, AST and CK-MB, especially at the dose of 250 mg/kg.Improvement in histological structures of cardiac, liver and renal tissues was shown in Kleinhovia sp. (250 mg/kg) treated rats, indicating a protective effect of the extract on doxorubicin acute toxicity. Abbreviations Used: DOX: Doxorubicin; CK-MB: creatine kinase-MB, AST: Aspartate transaminase; ALT: Alanine transaminase., Competing Interests: There are no conflicts of interest.