Docetaxel (DTX) has been used in cancer treatments for several decades, but it results in many adverse apoptotic effects through excessive production of reactive oxygen species (ROS) in some tissue including the kidney and testes. We aimed to investigate potential modulatory roles of melatonin (MEL) and selenium (Se) against DTX-induced apoptosis and oxidative injury in the testes and kidney of mice. Thirty-two mice were divided into four equal groups as control, DTX, DTX + MEL and DTX + Se. DTX group was treated with a single intraperitoneal dose of DTX. After DTX treatment, MEL and Se were administered to the mice in the DTX + MEL and DTX + Se groups for 7 days respectively. Increased lipid peroxidation, ROS, apoptosis, caspase-3 and caspase-9 activities in the kidney and testes of the DTX group were diminished by treatment with MEL and Se. DTX-induced decreases in vitamin E (alpha- and gamma-tocopherol), glutathione peroxidase and reduced glutathione levels in the kidney and testis were increased following MEL and Se treatments. In conclusion, our data show that MEL and Se can act as modulators against DTX-induced apoptosis and oxidative damage in the kidney and testis through up-regulation of glutathione and vitamin E and down-regulation of caspase pathways.