Quinolone antibiotics are a crucial class of synthetic antibacterial agents, widely utilized due to their broad spectrum of antibacterial activity. Due to the development of antimicrobial resistance, the potency of quinolone drugs decreased. Many conventional methods have been developed to elevate amination rate and to improve yield. These methods are generally characterized by prolonged reaction durations, high boiling solvents, harsh conditions, costly reagents and excessive heat generation, which have adversely affected the therapeutic efficacy of these compounds. Recently, green chemistry has focused on sustainable chemistry-dependent quinolone analogue synthesis methods that significantly reduce bacterial infections. These methods include one-pot synthesis, photoredox catalysis, phase transfer catalysis, ultrasonic irradiation, microwave-assisted, green solvent and catalyst-free synthesis, which often utilize energy-efficient, non-toxic and less time-consuming techniques, aligning with green chemistry principles to improve safety and environmental impact. Researchers continuously explore innovative approaches to applying these methods in synthetic reactions. This review includes a comprehensive analysis of synthetic literature from the past 15 years from Scopus, PubMed, Embase and WOS using keywords, such as green chemistry, quinolone and antibacterial, highlighting significant advancements and emerging trends. This work's importance lies in its extensive literature overview on green synthesis methods for quinolones and related heterocyclic compounds. Furthermore, to provide useful information for the generation of future antibacterial drugs, some structural-activity relationship studies and in silico studies have also been included to investigate the stable binding interactions between quinolone leads and various target proteins., (© 2025 Wiley‐VHCA AG, Zurich, Switzerland.)