Owing to the widespread emergence and proliferation of antibiotic-resistant bacteria, the therapeutic benefits of antibiotics have been reduced. In addition, the ongoing evolution of multidrug-resistant pathogens poses a challenge for the scientific community to develop sensitive analytical methods and innovative antimicrobial agents for the detection and treatment of drug-resistant bacterial infections. In this review, we have described the antibiotic resistance mechanisms that occur in bacteria and summarized the recent developments in detection strategies for monitoring drug resistance using different diagnostic methods in three aspects, including electrostatic attraction, chemical reaction, and probe-free analysis. Additionally, to understand the effective inhibition of drug-resistant bacterial growth by recent nano-antibiotics, the underlying antimicrobial mechanisms and efficacy of biogenic silver nanoparticles and antimicrobial peptides, which have shown promise, and the rationale, design, and potential improvements to these methods are also highlighted in this review. Finally, the primary challenges and future trends in the rational design of facile sensing platforms and novel antibacterial agents against superbugs are discussed.