Antimicrobial drug resistance in Neisseria gonorrhoeae has been documented all over the world. However, the situation in Sub-Saharan Africa has received little attention. It is critical to establish diagnostics and extend surveillance in order to prevent the emergence of illnesses that are resistant to several treatments. Monitoring antimicrobial susceptibility is critically required in order to gather data that may be utilised to produce treatment recommendations that will result in effective therapy, a decrease in gonorrhoeae-related difficulties and transmission, and effective therapy. Government authorities may set research and preventive objectives, as well as treatment recommendations, using data from the Gonococcal Antimicrobial Surveillance Program (GISP). Local and state health authorities may use GISP data to make choices about the allocation of STI prevention services and resources, to guide preventative planning, and to disseminate information about the most successful treatment practices. Using molecular and culture approaches, we investigated the occurrence of antibiotic resistance in isolates from KwaZulu Natal, South Africa. The great majority of gonococcal isolates (48% showed absolute resistance to ciprofloxacin), with penicillin and tetracycline resistance rates of 14% each. Only one of the gonococcal isolates tested positive for azithromycin resistance, with a minimum inhibitory concentration (MIC) of 1.5 µg/mL. Ceftriaxone was effective against all gonococcal isolates tested.