Mining activities play a crucial role in economic development; however, they are also recognized as one of the major sources of environmental degradation, particularly affecting ecosystems and wildlife habitats. Soil and water contamination by heavy metals, habitat destruction, and disruption of food chains are among the most significant environmental consequences of mining activities. In recent years, advances in biotechnology and genetic engineering, including the development of transgenic microorganisms and plants, have provided innovative and sustainable solutions to mitigate these adverse impacts. This comprehensive review examines recent progress in biotechnological applications such as biomining, bioremediation, and microbial-induced mineralization, with a particular focus on the use of transgenic organisms to reduce mining-related environmental pollution. The role of these approaches in decreasing heavy metal bioavailability, improving soil and water quality, and protecting wildlife ecosystems is critically discussed. Additionally, biosafety concerns, ecological risks, and regulatory challenges associated with the environmental release of transgenic organisms are addressed. Overall, biotechnology-based strategies offer promising tools for sustainable environmental management of mining-affected ecosystems. When combined with appropriate risk assessment and regulatory frameworks, these approaches can significantly contribute to biodiversity conservation and the protection of ecosystem health in mining regions.