Factros such as gene mutation and transfer, some inappropriate uses and diagnostics, and the prescription of antibiotics to undiagnosed patients has significantly led to the emergence of drug resistance in bacteria, which is also hampering our ability to treat infections. As the declines of new antibiotics, scientists and researchers keep trying to develop or propose some synergistic combinations of antibiotics with medicinal plants extracts in an effort to boost their antimicrobial activities against drug resistant bacteria. This work aimed to develop a cocktail regimen, which will be highly susceptible to confirmed drug resistant clinical isolate of Salmonella spp, using Tetracycline, Co-trimoxazole, Aspirin, Psidium guajava and Syzygium aromaticum extract alongside minimizing toxicity potential. Twenty-four (24) different combinations were made from 10 µg/mL of Co-trimoxazole, Tetracycline and Aspirin with each clove extract and separately again with guava extract. Eighteen (18) of them were combined in three different stages (6 each) using concentrated Tetraoxosulphate (vi) acid (H2SO4) and 0.1 Molar sodium hydroxide (NaOH), while 31 antimicrobial disks were prepared and tested on Salmonella spp. The antimicrobial susceptibility test revealed that Scl, a stage 1 combination of Co-trimoxaazole with clove extract; Ac2, a stage 2 combination of Aspirin and clove extract; Ag2,  a stage 2 combination of Aspirin and guava leave extract were all susceptible to the confirmed resistant isolate of Salmonella spp. Ag2 had the best zone of inhibition better than Ciprofloxacin inhibition zone at 20 µg/mL. Aspirin was the best precursor drug which favourably combines with both clove and guava extract to give a desired cocktail regimen with potential antimicrobial characteristics. Hence, it is needed to identify the compounds obtained in this combinations, isolates, and purify their active principles, and subjected to other pharmacological test to ascertain if they can be used to combat multi-drug resistant bacteria and other pathogenic organisms.