Extremophiles are the organisms that survive the harshest and extreme environments on earth, notably deep-sea sediments, permafrost, deserts, hypersaline water, etc., of the extremophiles, various fungal species like Aspergillus spp., Emericella spp., Eutypella spp., Microsporum spp., Penicillium spp., Trichoderma spp., Wallemia spp., etc. produce a number of bioactive molecules categorized into polypeptides, polyketides, terpenoids, alkaloids, sterols, etc. These metabolites are proven to possess antibacterial, antiviral, antifungal, anti-inflammatory, anticancer, and anti-diabetic activities. These compounds have significant scope in biomedical research and can be explored as potential candidates for new drug discovery. Apart from it, they can be substantially applied in the fields of environmental, industrial, and food technology. There is a need to isolate, propagate, and conserve these novel microorganisms and their active metabolites. This chapter provides an overview of various bioactive molecules obtained from different genera of extremophilic fungi isolated from extreme habitats on this planet. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.