The wetland ecosystem is known to possess unique vegetation and serves multiple functions within the environment. In this study, bacterial bioprospecting of bulrush rhizospheres in the Zhalong Wetland, China, was performed using comprehensive methods, including strain isolation and phylogenetic analysis, PCR detection of biosynthetic gene clusters, assessment of antimicrobial activity, metabolite profiling and genome analysis. A total of 27 actinobacterial strains were isolated, and their biosynthetic gene clusters (NRPS, PKS-I and PKS-II) were investigated; all of the tested strains had at least one of the three aforementioned biosynthetic gene clusters. Furthermore, fermentation broth extracts produced by these strains showed antimicrobial activities against certain pathogens, and ten of the extracts exhibited broad-spectrum antimicrobial activity. Liquid chromatography-mass spectrometry (LC-MS) analysis indicated chemical diversity of secondary metabolites from these extracts. Among these strains, ZLSD-24 generated the largest amounts and types of secondary metabolites. Subsequent genome analysis showed that 41 secondary metabolite biosynthetic gene clusters were present in the strain ZLSD-24, which was in accordance with the LC-MS data. Taken together, the results of this study reveal that bulrush rhizosphere habitat in the Zhalong wetland is a promising source of novel natural products.