Due to natural factors and human activities, ancient murals, stone carvings and other precious cultural heritages tend to suffer from widespread diseases such as disruption, salt efflorescence crusting, powdering, weathering, sootiness and pollution. The research and development of corresponding conservation and restoration materials and technology has long been a focus in the field of cultural relic protection. In recent years, bio-nano materials and biotechnology have become supplemental or alternative measures to conventional physical and chemical counterparts due to their superiority with regard to environmental friendliness, compatibility and applicability, and better conservation effects. This study systematically summarizes and sorts out the development context and state of application of functional microorganisms, biological enzymes, metabolites and innovative biotechnology with regard to the conservation and restoration of cultural heritages. These studies focus mainly on the latest research progress, as well as challenges of biological cleaning and reinforcement technology. They provide reference for scientific researchers to carry out innovative research on the conservation and restoration of cultural relics based on biotechnology.