The rapid emergence of resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics, therefore, there is a need for a systematic approach to the menace of resistant bacteria. Green synthesized nanoparticle (NPs) of medicinal plant based as become an alternative way out to total eradication of resistant microorganisms, Therefore, the search for new, effective bactericidal agents is imminent significantly, for combating drug resistance microorganism. This research work aims to isolate, identify and characterize endophytic bacteria from five non-leguminous plants, namely Carica papaya, Helianthus annuus, Talinum fruticosum, Phoenix dactylifera, and Solanum lycopersicum. The surface of the plants were sterilized, Isolation, characterization and identification using biochemical characterization of the endophytic bacteria were examined according to Bergey’s manual of Systemic Bacteriology. The sulfur/medicinal plant mediated Nanoparticle with and without Ocimum gratissimum were tested against the endophytic bacteria and selected clinical isolates, for their antimicrobial susceptibility test as described Kirby-Bauer Disc diffusion method. SNP1 was prepared from sodium thiosulfate penthahydrate, citric acid, with fresh leaves of O. gratissimum and characterized by using Shimadzu UV-VIS-NIR Spectrophotometer UV-3100 with a MPCF-3100 sample compartment while SNP2 was prepared using the same method but without O. gratissimum. The endophyte showed resistant to cephalosporin antibiotics family and SNP2, while all the endophytic bacteria were susceptible to ciprofloxacin (100%), pefloxacin (100%). Streptococcus infectinalis and Cellumonas flavigena showed high susceptibility to sulfur/ plant nanoparticle mediated with Ocimum gratissimum extract (SNP1). The study showed that sulfur/medicinal plant mediated nanoparticle can be a promising antimicrobial agent against a wide range of pathogenic and multiple drug resistance bacteria including both clinical isolates, its uses and practice should be encouraged especially against multiple drug resistance bacteria.