Five 2-(2-hydroxyphenyl)-5-phenyl-1,3,4-oxadiazole (HOXD) derivatives have been designed to explore their optical, electronic, and charge transport properties as charge transport and/or luminescent materials. The calculation results showed that the absorption and fluorescence wavelengths of derivatives have bathochromic shifts compared with those of HOXD. The derivatives with benzo[c]thiophene (2), benzo[d]thiazole (3), benzo[d]thieno[3,2-b]thiophene (4), and thieno[3,4-b]quinoxaline (5) fragments are expected to be promising candidates for electron transport materials. Furthermore, the derivatives 2 and 5 have better hole- and electron-transporting balance and can act as nice ambipolar materials. Derivative with benzo[c][1,2,5]thiadiazole fragment (1) and 2-5 can emit phosphorescence, which can enhance the electroluminescent efficiency that is the demanding factor for electroluminescence materials of OLEDs in flat panel display technologies. In addition, the derivatives 3 and 4 are promising luminescent materials for organic light emitting diodes (OLEDs) as well.