Microorganisms such as pathogens from humans, pets, and plants, as well as bacteria, fungi, and viruses, can cause damage in indoor environments, leading to infections and allergies. Additionally, the presence of indoor microorganisms can result in food contamination and economic damage, along with odors, corrosion, discoloration, and damage to facilities, equipment, and buildings. Therefore, a hygienic approach that includes research on microorganisms in indoor environments should be taken for their management. However, past approaches to indoor microorganism management have been limited to measuring the concentration of airborne bacteria and mold as stipulated in the Ministry of Environment’s Indoor Air Quality Act. Due to the COVID-19 pandemic, interest in microorganisms in indoor environments has been on the rise, along with demands to mitigate the damage they create. Because microorganisms have varying degrees of impact on the environment and organisms, they are classified by risk level and require secure research facilities tailored to target biosafety levels. However, there is a lack of awareness of the application of facilities and biosafety to study indoor microorganisms existing in indoor environments. Accordingly, in this study, both domestic and international biosafety regulations were reviewed, the harmfulness of indoor microorganisms was evaluated, and considerations for handling indoor microorganisms in domestic universities, companies, and public institutions were proposed.