Microbial infections and stress-related diseases are major contributors to human mortality, and current treatments face numerous challenges owing to microbial resistance and multidrug-resistant strains. As a result, there has been a shift towards bioactive compounds from natural resources, such as biodiversity-rich mangrove ecosystems. Mangroves are unique ecosystems with high salinity and organic matter that support rich biodiversity. With advancements in science and technology, it is prophesied that there is an increasing demand for new bioactive compounds from actinobacteria, including those from mangroves, which serve as repositories for organisms capable of producing diverse bioactive and therapeutic metabolites. The exploration of bioactive compounds from mangrove actinomycetes presents a frontier in pharmaceutical research as there is an urgent need for novel therapeutic agents. Among actinobacteria, Streptomyces species are particularly noteworthy for their production of bioactive metabolites, such as antimicrobials, antioxidants, anticancer agents, and neuroprotective compounds. This chapter emphasizes the importance of mangrove forests as rich reservoirs of microbial diversity and as promising bioprospecting hotspots for the isolation of actinomycetes. Additionally, it highlights potent bioactive metabolites from various actinomycete species and their therapeutic applications. Understanding the importance of these ecosystems is crucial for their preservation and the development of new molecules to control pathogens that may impact human, animal, and environmental health.