[Objective] The present work aims to screen cultivable microbes and bioactive metabolite producing bacteria in the gut of Sipunculus nudus from different areas of Beibu Gulf, so as to provide theoretical support for the subsequent development and utilization of gut microbial metabolites of Sipunculus nudus. [Methods] We isolated cultivable microbes from Zhanjiang, Beihai and Fangchenggang by plate and streak cultivation, and identified those microbes according to 16S rRNA gene sequence analyses. Meanwhile, we investigated the extracellular bioactive metabolites producing bacteria by transparent ring method, visible spectrophotometer and inhibition zone methods. [Results] We successfully screened 12 cultivable microbial genera from the gut of Sipunculus nudus in three Beibu Gulf regions, including Vibrio, Shewanella, Pseudomonas, Photobacterium, Bacillus. Vibrio is the dominant bacterium among the three regions. The strains producing extracellular protease, chitosanase, polysaccharide and bacteriostatic activity were mainly from Pseudomonas, Photobacterium, Bacillus. [Conclusion] There are significant differences on the bacteria genus level among the gut of Sipunculus nudus from different area of Beibu Gulf in China. Meanwhile, the cultivable symbiotic microorganisms of Sipunculus nudus can produce various extracellular active substances, which indicated that Sipunculus nudus is a good source of marine bioactive metabolites.