Novel antimicrobial agents are continually developed to address the global threat of multidrug-resistant Neisseria gonorrhoeae. Promising candidates include zoliflodacin and, possibly, solithromycin. We evaluated their in-vitro activities against gonococcal isolates collected in Korea. In total, 250 N. gonorrhoeae isolates obtained across Korea between 2016 and 2018 were used to determine the minimum inhibitory concentrations (MICs) of 10 therapeutic agents using the CLSI agar dilution method. Most isolates (94.8%, 237/250) demonstrated non-susceptibility to penicillin G, tetracycline, and ciprofloxacin, and susceptibility to ceftriaxone and spectinomycin was substantially high. The half-maximal IC (MIC50) and 90% IC (MIC90) values for zoliflodacin were 0.03 and 0.06 µg/mL, respectively; 0.06 and 0.12 µg/mL, respectively, for solithromycin; and 0.03 and 0.12 µg/mL, respectively, for ceftriaxone. Notably, no cross-resistance was observed between zoliflodacin and ciprofloxacin, despite both targeting DNA topoisomerase II enzymes. Zoliflodacin and solithromycin demonstrated significant in-vitro activity against multidrug-resistant N.gonorrhoeae isolates, and zoliflodacin has shown non-inferiority to ceftriaxone/azithromycin dual therapy in a clinical phase 3 trial. Collectively, our findings highlight the potential of zoliflodacin as a novel therapeutic agent for gonococcal infections, particularly in the context of rising multidrug resistance, and highlight the need for continued surveillance and development of alternative antimicrobial strategies.