Microbial infection of immune‐compromised corals influences disease severity, resulting in coral mortality. However, coral‐associated beneficial bacteria are known to produce antimicrobial compounds that prevent the growth of potential pathogens and invading microbes. Hence, beneficial bacteria associated with coral Porites lutea were isolated and antimicrobial protein and bioactive secondary metabolites were extracted and tested for their antimicrobial activity against putative prokaryotic and eukaryotic coral pathogens. Bioactive secondary metabolites exhibited remarkable antagonism against various coral pathogens such as Serratia marcescens, Vibrio species, and Aspergillus sydowii. Besides, the metabolites of Cobetia marina, Cobetia amphilecti, Pseudoalteromonas neustonica, and Virgibacillus halodenitrificans manifested notable inhibition against the protozoan ciliates (Uronema marinum, Holosticha diademata, Cohnilembus verminus, and Euplotes vannus) and zooplankton that are known to be involved in the secondary pathogenesis in coral diseased lesion progression. Thus, the present study may benefit in understanding coral‐associated beneficial bacteria for their antagonistic interactions with microbial pathogens, as well as their potential involvement in reducing coral disease severity.