Methotrexate is widely used as chemotherapeutic agent in the treatment of malignancies and inflammatory diseases. Meloxicam is an analgesic and antipyretic drug. This study was carried out to determine if Curcuma longa has an ameliorative effect against Methotrexate and Meloxicam-induced toxicity in different organs in rats. Sprague-Dawley rats weighing 170±20gm were divided into six groups. Methotrexate and Meloxicam significantly increased serum AST, ALT, urea, and creatinine, liver & kidney body weight ratio as well as malondehyde and significant decrease in glutathione and superoxide dismutase when compared with control group. Administration of curcumin one hour before Methotrexate and Meloxicam significantly improved all the parameters mentioned before. The histopathological alterations confirmed the biochemical results. The data revealed that curcumin administration improved the liver and kidney histopathological lesions in rats treated with Methotrexate and Meloxicam. This study concluded that curcumin has a partial protective effect against the toxicity of Methotrexate and Meloxicam.