Valproic acid (VPA) is a drug that is often used to treat epilepsy, seizures, and similar diseases. However, it is known to have serious toxic effects on the liver and the kidney. Oxidative stress and other metabolites of VPA have been suggested to be responsible for VPA induced hepatotoxicity and nephrotoxicity. We evaluated the possible protective role of royal jelly (RJ) against the effects of VPA through toxicity tests on livers and kidneys of rats. Twenty-four male albino rats were separated into three groups; group (1): healthy control received no drug, group (2): administrated VPA (500 mg/kg/day by oral gavage), group (3): received VPA (500 mg/kg/day by oral gavage) one hour prior to RJ (500 mg/kg/day by oral gavage). After two weeks, the rats' livers and kidneys were removed for histopathologic investigation with hematoxylin and eosin staining while biochemical assessment was performed on blood samples. The VPA group had a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, creatinine and pro-inflammatory cytokines (IL-1a, IL-1b and IL-6). Histopathological observations in liver and kidney tissues also were related with the biochemical parameters. VPA causes hepato-renal damage by promoting inflammation, oxidative stress, and fibrosis. RJ enhanced the functions of the liver and kidneys by reducing ALT, AST, urea and creatinine compared with the VPA treatment group and reduced serum pro-inflammatory cytokines. In addition, the histopathological impairment of liver and kidney tissues were reversed by RJ treatment. In conclusion, RJ can protect hepato-renal functions against VPA acid-induced organ damage.