Kilroot salt mine, a Triassic halite deposit located in County Antrim, Northern Ireland, is the only permanent hypersaline environment on the island of Ireland. In this study, the microbiome of this unstudied environment was profiled for the first time using conventional and enhanced culturing techniques, and culture independent metagenomic approaches. Using both conventional isolation plates and iChip devices, 89 halophilic archaeal isolates from six known genera, and 55 halophilic or halotolerant bacterial isolates from 18 genera were obtained, based on 16S rRNA gene sequencing. The archaeal isolates were similar to those previously isolated from other ancient halite deposits, and as expected, numerous genera were identified in the metagenome which were not represented among the culturable isolates. Preliminary screening of a selection of isolates from this environment identified antimicrobial activities against a panel of clinically important bacterial pathogens from 15 of the bacterial isolates and one of the archaea. This, alongside previous studies reporting the discovery of novel biocatalysts from the Kilroot mine microbiome, suggests that this environment may be a new, untapped source of of chemical diversity with high biodiscovery potential.