Despite the wide use of conventional antibiotics to treat bacterial infections, bacteria have now become resistant to many antibiotics and other antibacterial agents. This resistance is heritable and allows the spread of intractable bacterial infections, which is one of the biggest health challenges encountered around the world. This issue has led to the search for new therapeutic antibacterial agents. In the last few decades, nanomaterials, especially metal and metal oxide nanoparticles, have gained much attention due to their advatageous properties, including large surface-to-volume ratio and high antimicrobial activity. Among various metal and metal oxide nanoparticles, copper oxide nanoparticles have been particularly investigated owing to their biocompatibility and antibacterial activity against both Gram-positive and Gram-negative bacteria. Several antibacterial mechanisms have been proposed for copper oxide nanoparticles, among which their interaction with bacterial deoxyribonucleic acid and ribonucleic acid is considered important. These nanoparticles can disrupt the accuracy of DNA replication by changing in the DNA sequence that result in differences in the target sequences bound by random amplification of polymorphic DNA (RAPD) primers. This mini-review discusses this interaction according to recent studies.