The karst ecosystem, distinguished by its unique geophysical characteristics, hosts a wide variety of microbes. In these environments, cave-dwelling bacteria are renowned for producing compounds with diverse biological activities. Therefore, this study was conducted to explore the antibacterial potential of cave-dwelling bacteria from the Maros-Pangkep Karst Area in South Sulawesi, Indonesia. Soil samples were collected from Leang Kassi, Leang Jarie, and Leang Ulu Wae caves. The three caves are located at different points within the Maros-Pangkep karst system, each representing an independent and spatially separated sampling site. The bacterial isolation was performed, and antibacterial agar diffusion assays were conducted against pathogenic bacteria as a preliminary qualitative screening approach. The secondary metabolites from promising isolates were extracted using ethyl acetate and tentatively characterized using GC-MS. Additionally, the putative compounds were then screened and evaluated for their potential interaction with the protein target through molecular docking analysis as an in silico analysis approach. Results showed that isolates exhibited distinct morphological and antibacterial properties, with one from Leang Ulu Wae showing notable inhibitory effects in preliminary screening assays. 16S rRNA identified the Leang Ulu Wae isolate as Exiguobacterium. GC-MS analysis detected three major compounds with a library match (Similarity Index, SI) ≥90%. In silico analysis suggested that Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl), exhibited the most favorable predicted binding interaction with the protein target, followed by Cyclo(L-prolyl-L-valine) and 5,10-Diethoxy-2,3,7,8-tetrahydro-1H,6H-dipyrrolo[1,2-a]. The findings suggest that the bacteria located in the caves of the Maros-Pangkep Karst Area possess considerable potential for future antibacterial research.