This study aimed to determine the genetic diversity of antibiotics and plants extract resistant Staphylococcus aureus using molecular technique. A total of 106 human clinical samples were collected from patients in three different hospitals within Ekiti State. Microbiological and molecular analyses were performed using standard methods. Antimicrobial susceptibility test with common antibiotics and plant leaves extracts was carried out using disk and agar well diffusion methods. Urine samples

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... m male patients recorded high percentage of S. aureus (57.1%) as compared to the female patients (43.1%). Percentage of S. aureus recorded from the ear swab samples in male patients (58.3%) was also high as compared to the female (41.7%). From the nose swab samples, female patients recorded 60% as compared to their male counterpart (40%). Equal percentage (50%) of wound infection caused by S. aureus was observed in both male and female patients. Of the eight antibiotics used in this study, the S. aureus isolated were susceptible to ofloxacin (25 to 36 mm), gentamycin (16 to 23 mm) and erythromycin (11 to 25 mm). All the isolates confirmed resistance to ceftaxidime and cloxacillin. Nine isolates were susceptible to cefuroxime with zones of inhibition that ranged from 10 to 25 mm, while 11 were susceptible to ceftriaxone with zone of inhibition between 11 and 20 mm. Only one isolate was sensitive to augmentin (amoxicillin/clavulanate) with zone of inhibition of 20 mm. Out of three plant extracts used in this study, aqueous leaf extract of Terminalia catappa demonstrated highest antibacterial activity on the test isolates with zone of inhibition of 16 to 36 mm followed by Mangifera indica with inhibition ranging from 11 to 32 mm, while least inhibition ranging from 11 to 20 mm was exhibited by Acalypha wikesiena. Random amplified polymorphic DNA (RAPD) proved to be useful as genetic markers in determining genetic diversity among antibiotic and plant extract resistant S. aureus.