Introduction Cyanobacteria are important members of the dense biofilms that colonize available substrates in mangrove habitats worldwide. However, their taxonomic diversity and biological activities have received little attention. Methods The occurrence of cyanobacteria is evaluated in 27 biofilms collected from mangroves in Mayotte. Filamentous cyanobacterial strains were isolated and characterized using 16S rRNA comparative gene sequence analysis. LC-MS/MS experiments were performed on the crude extracts of the faster-growing strains, and construction of their molecular network showed a conspectus of their chemical diversity. Biological activities of the strain extracts were then evaluated using standard assays. Results and discussion Isolation procedures yielded 43 strains representing 22 species-level taxa, of which only three could be assigned to existing species. Some of these strains were among the most abundant cyanobacteria present in biofilms. PCR assays did not support the production of the major cyanotoxins. Analysis of metabolites from 23 strains using both in silico tools ISDB- DNP (In silico Data Base–Dictionary of Natural Products) and MolDiscovery, revealed occurrence of godavarin K, a limonoid natural product previously isolated from the seeds of an Indian mangrove tree. This annotation was further confirmed by the marine database MarinLit, suggesting that cyanobacteria might be an alternative source of godavarin K and its four isomers. While no significant antimicrobial and cytotoxic activities were observed, some strains exhibited anthelmintic and antibiofilm activities that warrant further investigation and may be relevant to biofilm ecology. Mangrove biofilms thus appear to be an untapped reservoir of novel culturable cyanobacterial lineages, with bioactivities relevant to their biofilm lifestyle, which may be of interest for bioinspiration.