Most microbial infectious diseases can be treated successfully with the remarkable array of antimicrobials current available; however, antimicrobial resistance, adverse effects, and the high cost of antimicrobials are crucial health challenges worldwide. One of the common efforts in addressing this issue lies in improving the existing antibacterial delivery systems. Solid nanoparticles (SNPs) have been widely used as promising strategies to overcome these challenges. In addition, oral delivery is the most common method of drug administration with high levels of patient acceptance. Formulation into NPs can improve drug stability in the harsh gastrointestinal (GI) tract environment, providing opportunities for targeting specific sites in the GI tract, increasing drug solubility and bioavailability, and providing sustained release in the GI tract. Here, we discuss SNPs for the oral delivery of antimicrobials, including solid lipid NPs (SLNs), polymeric NPs (PNs), mesoporous silica NPs (MSNs) and hybrid NPs (HNs). We also discussed about the role of nanotechnology in IV to oral antimicrobial therapy development as well as challenges, clinical transformation, and limitations of SNPs for oral antimicrobial drug delivery.