Background: Disinfectants and conventional antibiotics are used daily in Nigeria’s households and hospitals, in various approaches and at exceptional concentrations with inside to combat infectious diseases. The prevalence of antimicrobial resistance globally has made most chemotherapeutic agents less efficient to target pathogens. Aim: This research was done to determine the efficacy of some disinfectants and conventional antibiotics used against ESKAPE pathogens. Methodology: The in vitro efficacy of the disinfectants and antibiotics were compared using the disc diffusion (Kirby-Bauer) method. Results: Inhibition zone diameters were observed in all of the disinfectants and conventional antibiotics at concentration-dependent for the tested pathogenic isolates. Chloroxylenol was effective at higher concentrations and showed a progressive decrease in zones of inhibition as the concentration decreases. Ethanol was effective at 70% and 35% concentrations against Staphylococcus aureus. Hypochlorite was effective against Klebsiella pneumoniae, Pseudomonas aeruginosa, and E. coli at a 100% - 25% concentration and effective against Staphylococcus aureus at 100% and 50% concentrations. Therefore, the efficacy of disinfectants and antibiotics arise to be crucial however concentration-dependent. Conclusion: The results obtained from this study may be used as an alternative for medical applications. However, inappropriate disinfectant and conventional antibiotic use resulted in emergence of resistant microorganisms; hence these therapeutic agents should be used properly at a sufficient concentration to prevent diseases caused by these pathogenic bacteria. Nevertheless, the need to compare the efficacy of these disinfectants and conventional antibiotics against ESKAPE pathogens in vivo is very important.