In this study, for the first time, antimicrobial properties of Al–Cu–Fe, Al–Cu–Fe–B and Al–Cu–Fe–Co quasicrystal powders were investigated in the leached and un-leached condition against Gram-negative (E. aerogenes, K. pneumoniae) and Gram-positive (B. cereus, K. rosea) bacterial environment. Leaching of the powders in 10 M NaOH aqueous solution resulted in the enrichment of Cu and Fe at the surface. Consequently, bacterial activities in the vicinity of the leached quasicrystal powders were inhibited, indicating good antimicrobial characteristics of the leached powders. All the three leached powder samples exhibited antimicrobial activities with a varying degree. From the diameter of inhibition zone, it was deduced that E. aerogenes are the most susceptible against the leached powders. The leached Al–Cu–Fe–B and Al–Cu–Fe–Co quasicrystal powders showed nanostructured features on the outer surface. During leaching, the icosahedral structure was retained in all the samples.