Bacteria have been existing around the world for billions of years, with a vast living space. Throughout their evolutionary process, bacteria have been developing numerous defense mechanisms against environmental threats, enhancing their ability to survive and proliferate. Bacteria developed the enzymes that could destroy penicillin shortly after its discovery; this prompted the scientific community to investigate the defense mechanisms present in bacteria. Bacteria have various defense mechanisms, including the cell membranes, capsules, efflux pump systems, target modification, motility, biofilms, quorum-sensing signals, secretion systems, bacteriocins, base and nucleotide excision repair systems, neutralization, and restriction-modification systems that led to advancements in recombinant DNA technology. Understanding the foundation of bacterial defense strategies is crucial not only for uncovering antimicrobial defense mechanisms encountered in medical microbiology practice but also for understanding bacterial biology and anti-phage mechanisms. Bacterial defense mechanisms are examined elaborately in this review article.