One of the most significant problems of the twenty-first century is the appearance and rapid evolution of multiple drug-resistant (MDR) bacterial strains. The emergence of resistance towards available drugs poses a growing threat to global public health. Unfortunately, developing new antibiotics is a tedious and difficult challenge, urging the research community to strive for unusual clinical targets with a different mode of action. The antivirulence strategy disarms pathogenic bacteria and attacks the virulence factors. Type III secretion system (T3SS) facilitates virulence in many pathogenic gram-negative bacteria. T3SS is considered an effective needle-syringe mechanism associated with humans, plants, and animal hosts to inject effectors inside the cytosol of host cells. This review focuses on T3SS, its assembly, and visualization, along with presently developed small molecules, peptides, and antibodies to inhibit the complex. Evaluation of the effectiveness of compounds is in progress on animal models, and promising studies are being conducted to develop antibodies and vaccines that target T3SS. Reports published till now specify that T3SS inhibitors can evolve into innovative antibacterial therapy, bringing about a revolution in the pharmaceutical world. Apart from this, to get a better understanding of the mechanism at the molecular level, the functioning of T3SS in Salmonella is also discussed.