Rational design and scalable construction of antibacterial mediators based on unique graphene architectures with highly efficient antibacterial ability and significant biocompatibility are challenging. Herein, sulfur-doped graphene skeletons uniformly decorated with metal oxide nanoparticles were designed and constructed via one-step laser-induced microexplosive techniques and demonstrated for the first time as highly efficient antibacterial agents. The optical density and flat colony counting methods demonstrated that the as-designed laser-induced MoOx/sulfur-doped graphene hybrids exhibited exceptional activity inhibition of Escherichia coli and Staphylococcus aureus. Moreover, the bacteria were treated with an impressive laser-induced MoOx/sulfur-doped graphene colloidal solution of concentration as low as 1 mg/mL for 4 h, leading to an excellent viability loss of 85% for the two bacteria. Cell toxicity experiments proved that the biological toxicity of laser-induced MoOx/sulfur-doped graphene to pig sperm cells was negligible. The molecular dynamics calculations proposed that the intrinsic interaction with N-acetylglucosamine at the cell wall and the high-efficiency synergistic effect of sulfur-doped graphene and MoOx played the key role in inhibiting the viability of bacteria. This work provides new insights for a novel structure design and opens up a potential route to construct antibacterial agents with high efficiency for clinical application.