Rapid development of antibiotic resistance of bacteria and fungi, as well as cancer drug resistance, has become a global medical problem. Therefore, alternative methods of treatment are considered. Studies of recent years have focused on finding new biologically active compounds that may be effective against drug-resistant cells. High biodiversity of hard-to-reach environments offers sources to search for novel molecules potentially applicable for medical purposes. In this review article, we summarize and discuss compounds produced by microorganisms from hot springs, glaciers, caves, underground lakes, marine ecosystems, and hydrothermal vents. Antibacterial, antiviral, antifungal, anticancer, anti-inflammatory, and antioxidant potential of these molecules are presented and discussed. We conclude that using compounds derived from microorganisms occurring in extreme environments might be considered in further studies on development of treatment procedures for diseases caused by drug-resistant cells.