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Recently, the emergence of antimicrobial-resistant bacterial infections has been considered one of the global health crises that threaten communities. The rise and dissemination of resistance within bacterial pathogens make the effectiveness of antibiotics decline gradually over time. As a result, the search for novel antibiotics from different natural sources has increased. Some microorganisms are able to produce secondary metabolites for protection. Bacteria, for example, have the ability to yield antibiotics. One important habitat that has yet to be fully exploited for antibiotic-producing bacteria is geothermal springs. Hot springs have been used for spas as well as for treating dermatological infections. Thirty-two water samples were collected from six different hot springs in Saudi Arabia. Several biological and microbiological assays were used to assess the antibacterial activities of samples against antimicrobial-resistant- and susceptible-bacterial strains and identify the genus and species of antibiotic-producing bacteria. Moreover, chromatographic and spectroscopic techniques were utilized to isolate the active compounds, and aid structural elucidation. The cross-streak assay's findings illustrated that there were 14 bacteria with antimicrobial activities against most of the resistant- and susceptible-bacterial strains. 16S rRNA gene sequencing demonstrated that all antibiotic-producing bacteria to be Bacillus species; Bacillus paralicheniformis (6), Bacillus licheniformis (2), Bacillus pumilus (5) and Bacillus cereus (1). Seven compounds were isolated from these bacteria: five of which were known and two compounds were novel. The outcomes of MIC assay showed that all isolated compounds had mild to moderate antibacterial activities (between 128 µg/mL and 512 µg/mL in compared to the control) against all tested strains except for one compound (cholesterol (OM2)), which had no activity. The other known compounds were phenylacetic acid (OM7), isovaleric acid (OM4), ethyl-4-ethoxybenzoate (OM5) and N-acetyltryptamine (OM1). The two new compounds were N1-(N,N-dimethylcarbamimidoyl)-N1-methylterephthalamide (OM3) that belongs to the guanidine class of antibiotics, which are commonly isolated from microbes and 3-methyl-2H,7H-pyrano[2,3-b]pyran-2,7-dione (OM6), coumarin-like structures, which are also known for their antibacterial activities. In summary, this is the first study to investigate antibiotic-producing bacteria from hot thermal springs in Saudi Arabia. Screening revealed the propensity to isolate Bacillus spp., which are known to produce antibiotics in other habitats, particularly soil and aquatic environments. New compounds of known antibacterial classes could be isolated illustrating the potential of hot thermal springs as a source of discovering antibiotics.