The rapid spread of antimicrobial resistance (AMR) severely limits treatment options and poses a significant threat to healthcare. Misuse of antibiotics, rapid transmission through plasmids, and the slow pace of new antibiotic discovery exacerbate this issue. The rampant evolution of AMR increases the treatment gap, affecting healthcare facilities, the economy, and security. The current AMR burden demands an urgent need to revisit contemporary antimicrobial research. Notably, microbial nanoparticles offer promising alternatives with targeted drug delivery and efficient immune response modulation. Carbon-based nanostructures and metallic/metal oxide nanoparticles have unique characteristics that make them effective in combating AMR. Upon penetrating microorganisms, they employ multiple mechanisms to exert bactericidal and antibiofilm activity. The generation of reactive oxygen species (ROS) is the central process, initiating a cascade of effector signaling within the microbes, leading to significant metabolic rewiring and altered respiration. Hence, microbial nanomaterials are increasingly being used in pharmaceutical, food packaging, and textiles industries. Although microbial nanomaterials are less toxic, their bioaccumulation-mediated toxicity still remains an issue. Nevertheless, these tiny titans have strengthened the armamentarium of antimicrobials, offering a promising avenue for combating AMR and improving public health outcomes.