Due to the nascency of synthetically derived biological systems, there is a need to develop protocols for safety and security management. These protocols can be adapted from existing safety and security protocols (e.g., Biosafety Level Classification of biological agents) as well as NASA’s and ESA’s planetary protection guidelines. Currently, NASA is preparing for its first sample return mission from Mars including determining how to manage the types of hazards that may be returned to Earth. Synthetic biology can look to risk management practices from related disciplines, and NASA can look to its established protocols from lunar exploration as it strives to minimize Mars sample return bio-risk. Notably, the biosafety concerns of synthetic cell research are very similar to those of planetary back-contamination from extraterrestrial samples. Thus, the measures taken to limit planetary back-contamination can serve to help develop biosafety protocols for synthetic cell research. We summarize existing tools used in planetary protection that can be repurposed to establish protocols for synthetic cell safety and security.