Different resistance mechanisms are involved in exhibiting resistance to different groups of antibiotics. Researchers are searching for new therapeutic options to encounter the emerging trend of microbial resistance. Bacteria were isolated from the extreme environment of Cholistan Desert and were screened for characterization. Potential metabolites that showed broad-spectrum activity were partially purified using silica gel chromatography and determined their minimum inhibitory concentration. A collection of 50 bacterial isolates from soil samples was screened for metabolite production and among them isolate R19 of Bacillus sp. and isolate A8 of Alcaligenes sp. had high similarity with strong antimicrobial metabolite producers. The growth of A8 was stable at slight acidic pH while R19 was best at neutral pH. Similarly, the best growth of A8 was observed at 37 °C while R19 at 35 °C. Minimum inhibitory concentration of purified compounds of Bacillus sp. were determined at concentration range of (3.12 – 100 %) against multidrug-resistant (MDR) strains of Shigella, Enterobacter aerogenes, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumonia and produced 10 – 25 mm zone of inhibition. Metabolites of Alcaligenes sp. were sufficient to inhibit the growth of all selected MDR bacteria at concentrations 12.25 – 100 % and shows 10 – 20 mm zone of inhibition. Bacillus sp. and Alcaligenes sp. can be used as producers of potential antibacterial metabolites. Proper utilization of selected metabolites can be helpful in combating emerging drug resistant pathogenic bacteria. In addition, further proteomic analysis and structural insight should be considered to elaborate their active ingredients and its efficacy.