Bacterial infections represent a significant health threat globally, and are responsible for the majority of hospital-acquired infections, leading to extensive mortality and burden on global healthcare systems. The second generation fluoroquinolone ciprofloxacin which exhibits excellent antimicrobial activity and pharmacokinetic properties as well as few side effects is introduced into clinical practice for the treatment of various bacterial infections for around 3 decades. The emergency and widely spread of drug-resistant pathogens making ciprofloxacin more and more ineffective, so it's imperative to develop novel antibacterials. Numerous of ciprofloxacin derivatives have been synthesized for seeking for new antibacterials, and some of them exhibited promising potency. This review aims to summarize the recent advances made towards the discovery of ciprofloxacin derivatives as antibacterial agents and the structure-activity relationship of these derivatives was also discussed.