BiSe with intrinsic low thermal conductivity has considered as a promising thermoelectric (TE) material at nearly room temperature. To improve its low thermoelectric figure of merit (zT), in this work, Sb and Te isovalent co-alloying was performed and significantly optimized its TE property with weakly anisotropic characteristic. After substituting Sb on Bi sites, the carrier concentration is suppressed by introduction of Sb- Se site defects, which contributes to the increased absolute value of Seebeck coefficient (|S|). Further co-alloying Te on Se of the optimized composition Bi_0.7Sb_0.3Se, the carrier concentration increased without affecting the |S| due to the enhanced effective mass, which leads to a highest power factor of 12.8 μW/(cm·K²) at 423 K. As a result, a maximum zT of ~0.54 is achieved for Bi_0.7Sb_0.3Se_0.7Te_0.3 along the pressing direction and the average zT (zT_ave) (from 300 K to 623 K) are drastically improved from 0.24 for pristine BiSe sample to 0.45. Moreover, an energy conversion efficiency ~4.0% is achieved for a single leg TE device of Bi_0.7Sb_0.3Se_0.7Te_0.3when applied the temperature difference of 339 K, indicating the potential TE application.