Chlorpyrifos (CPF) is an extensively used and effective broad-spectrum organophosphorus insecticide. CPF exposure elicits liver injury mediated via oxidative stress; it disrupts the oxidant/antioxidant detoxification system, which consequently causes hepatotoxicity. Jojoba is widely used as a medicinal plant cultivated worldwide. Jojoba oil, extracted from Jojoba seeds, contains a high percentage of phenols and flavonoids, which make it a powerful antioxidant and enable it to get rid of free radicals. Therefore, the current investigation aimed to evaluate the potential protective and therapeutic effects of Jojoba oil against the oxidative effect of chlorpyrifos-induced hepatotoxicity in rats. Thirty adult male albino rats were divided into five groups of six animals in each group. Control group, Jojoba group, CPF-administration group, Jojoba prophylactic group, and Jojoba therapeutic group. Blood samples and hepatic tissues were obtained from each rat for biochemical and histopathological examinations. Results indicated that CPF-induced hepatotoxic effects were evidenced by elevated serum alkaline phosphatase and γ-glutamyltransferase, with histopathological alterations in hepatic tissue. Additionally, our results showed involvement of oxidative stress in liver injury after intoxication with CPF manifested by increased malondialdehyde level and decreased superoxide dismutase and catalase activities in hepatic tissues. Conversely, these results were reversed by Jojoba oil administration. Collectively, our data indicated that Jojoba oil can alleviate CPF-induced oxidative stress in hepatic tissues and reduce histopathological alterations. In conclusion, Jojoba oil could provide significant protective and therapeutic effects against CPF-induced hepatotoxicity, making it a potentially advantageous natural protective and therapeutic agent.