Mangrove plants, which grow in tropical and subtropical coastal areas, are known hosts to many plant species with remarkable bioactivity. This chapter highlights the available phytochemical composition of mangrove plants and their significant potential for antimicrobial activity, hence explaining their medicinal importance. The mangrove plants have adapted themselves to live in conditions of high salinity and low oxygen by producing distinctive secondary metabolites like steroids, triterpenes, saponins, flavonoids, alkaloids, and tannins, which show antimicrobial, anti-inflammatory, and antioxidant activities. Secondary metabolites of mangroves disrupt the microbial cell membrane, block the biosynthesis of nucleic acids, and break off their metabolic pathways, so killing the pathogens. The most prominent among such mangrove species are Avicennia marina, Rhizophora mucronata, and Bruguiera cylindrica, which have great prospects against multidrug-resistant bacteria; and thus as good sources of novel antibiotics. With the surge in the demand for alternative drug agents, mangrove-derived compounds come out as the key addresses of antimicrobial resistance. This chapter highlights the need for more research to further explore the medicinal potential of mangrove plants and makes a strong statement about the importance of conservation for sustainable healthcare innovations.