Natural products (NPs) are secondary metabolites that exert their biological effects within organisms and on other organisms. Among the microbial consortia, bacteria have been demonstrated to be potent microbial producers of bioactive natural therapeutic products due to their versatile biocatalytic activity. Therefore, the present study encompasses the isolation, identification, and characterization of four novel bacterial strains that exhibited the potential to produce natural therapeutic products. The novel cadre of the isolates was determined via taxonomical assessment, employment of myriad biochemical, antagonistic screening tests, followed by 16S rRNA molecular characterization, and bioinformatics analysis, which allowed the naming of the subsequent isolates as, Klebsiella pneumoniae strain ABSKALAB01, Klebsiella quasipneumonia strain ABSKSLAB02, Streptomyces minutiscleroticus strain ABSKSLAB03, and Streptomyces peucetius strain ABSKSLAB04, and was deposited in the GenBank under accession numbers ‘OP597532’, ‘OP597545’, ‘OQ061473’ and ‘PP086938’, respectively. Media optimization via OVAT approach, and statistical optimization via Plackett–Burman and RSM-mediated Box–Behnken designs were also conducted to assess the antagonistic, and NP-producing potential, followed by the construction of the secondary structure of 16S rRNA. The results signified that the subsequent bacterial strains hold the potential to produce natural therapeutic products in diacritic conditions, and the Streptomyces peucetius strain ABSKSLAB04 demonstrated the highest NP-producing potential among all the other isolates. The study also signifies the subsequent isolates can further be utilized for industrial-driven investigations.