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According to the CDC, there are more than 2.8 million antibiotic resistant infections occurring in the United States each year, and more than 35,000 people die as a result (CDC 2019). Furthermore, the CDC classifies a group of bacteria known as ESKAPE pathogens as six emerging antibiotic-resistant pathogens that are difficult to eradicate with current antibiotics. Our study aims to identify and characterize soil-derived microorganisms with the potential to produce antimicrobial compounds effective against safe relatives of ESKAPE pathogens, with the goal of translating these findings to combat their pathogenic counterparts. We hypothesize that bacteria identified from the soil will inhibit the growth of the following nosocomial associated safe relatives Bacillus subtilis for E. faecium, Staphylococcus epidermidis for S. aureus, Escherichia coli for Klebsiella pneumoniae, Acinetobacter baylyi for A. baumannii, Pseudomonas putida for P. aeruginosa, and Enterobacter aerogenes for Enterobacter species. To test our hypothesis, soil samples were collected from Fayetteville State University (FSU) campus and serially diluted onto LB agar plates. Sixty-three distinct colonies were isolated and screened against non-pathogenic ESKAPE safe relatives. Of the 63 Fayetteville State University soil isolates (FSIs) screened, 12 (19%) exhibited antimicrobial activity against at least one of the six ESKAPE safe relatives, with all 12 inhibiting Acinetobacter baylyi and only FSI 15 demonstrating broad-spectrum inhibition. Characterization assays revealed that 11 of the 12 isolates were Gram-negative, catalase-positive, and motile; the single Gram-positive isolate (FSI 4) was catalase-negative and non-motile. All isolates displayed resistance to penicillin, while most remained susceptible to tetracycline and ciprofloxacin. These findings support our hypothesis that soil-derived bacteria can produce putative antimicrobial compounds effective against non-pathogenic ESKAPE safe relatives. This study underscores the potential of soil microbiota on the campus of Fayetteville State University as a source of novel antimicrobial agents capable of inhibiting antibiotic resistant ESKAPE pathogens and warrant further investigation into their therapeutic potential