Novel carbazole-oxadiazoles were developed as new potential antibacterial agents to combat dreadful resistance. Some target compounds displayed predominant inhibitory effects on the tested Gram-positive and -negative bacteria, and carbazole-oxadiazoles <b>5g</b>, <b>5i</b>-<b>k</b>, <b>16a</b>-<b>c</b>, and tetrazole analogues <b>23b</b>-<b>c</b> were found to be efficient in impeding the growth of MRSA and <i>Pseudomonas aeruginosa</i> ATCC 27853 (MICs = 0.25-4 μg/mL). Furthermore, compounds <b>5g</b> and <b>23b</b>-<b>c</b> not only possessed rapid bactericidal ability and low tendency to develop resistance but also exhibited low cytotoxic effects toward Hek 293T, HeLa, and red blood cells (RBCs), especially molecule <b>5g</b> also showed low toxicity in vivo, which showed the therapeutic potential of these compounds. Further exploration indicated that compounds <b>5g</b>, <b>5i</b>, and <b>23b</b>-<b>c</b> could disintegrate the integrity of bacterial cell membranes to leak the cytoplasmic contents, thus exerting excellent antibacterial effects. These facts mean that carbazole-based antibacterial agents might have bright prospects in confronting bacterial infections.