The overuse of antibiotics nowadays escalates the threat of antibiotic-resistant and multidrug-resistant bacterial infections. Piezoelectric materials are gaining interest for their unique properties of generation of reactive oxygen species (ROS) in an aqueous medium under mechanical stress that can decompose even drug-resistant pathogenic bacteria. In reality, the generated ROS ruptured the cell membranes, which enhanced the leakage of cellular components of pathogens and led to cell death. This versatile mechanism of bacterial disinfection can gain promising effectiveness and reduce the resistant development probability that commonly happens in other conventional therapeutic modalities. This work explores the potential application of piezoelectric materials in antibacterial effects. First, in this chapter, the bacterial degradation mechanism by piezocatalysis has been illustrated. Piezoelectric materials such as ceramics (lead zirconate titanate: PZT, barium titanate: BatiO 3 , bismuth ferrite: BiFeO 3 , ZnO), polymers (PVDF, PDMS, PTFE, PVA), and their bacterial decontamination efficiencies have been summarized. Moreover, the highlights have also been given on enhancing the efficiency for overcoming the multidrug-resistant (MDR) bacterial infections. Furthermore, this chapter addressed the challenges of piezoelectric materials, such as biocompatibility, scalability, and long-term stability, and their remediation strategies. Piezoelectric materials have opened a potent remedy for antibiotic resistance and MDR bacterial infection.