Mudskippers are important for ecotoxicological studies of coastal wetlands. They are recognized as a potential bio-indicator in estuarine water biomonitoring programs due to their natural abundance, high resistance to polluted environmental conditions, benthic habitat, high trophic levels in the aquatic food chain, and sensitivity to environmental changes. Mudskippers have the ability to accumulate heavy metals in their tissues and also have a strong propensity for determining the biological impact of pollutants on coastal wetlands. Hence, Mudskippers have the ability to serve as ideal sentinel organisms for the biomonitoring of heavy metal pollution. The application of biomarkers is very important for biomonitoring, as it is a direct indicator of all the toxic effects of heavy metals on organisms and is less expensive to use compared to chemical indicators, especially for heavy metal pollutants with very low concentrations. Biomarkers responses such as genotoxicity and immunotoxicity have not been applied as diagnostic tools to monitor the effect of heavy metals on mudskippers, while oxidative stress biomarker is widely used to diagnose and evaluate the adverse effects of heavy metals on mudskippers. So, these biomarkers need to be developed for more comprehensive information on the heavy metal toxicity in fishes. Thus, oxidative stress, genotoxicity, and immunotoxicity biomarkers can be incorporated into standard biomonitoring programs as new studies and approaches to resolve the global issue of heavy metal pollution in estuaries and the degradation of coastal wetland ecosystems.