With human missions to Mars becoming realistic, primary care physicians may soon be called upon to act as crew medical officers (CMOs). This role would extend GPs’ responsibilities to include bioethical decision-making around potential exposure to Martian microbes, containment breaches, and planetary protection. This review explores how existing literature across primary care, ethics, and space medicine can inform this emerging challenge.To assess and synthesize academic and policy literature that supports the ethical, clinical, and operational role of GPs in scenarios involving planetary protection and interplanetary microbial exposure.We conducted a structured review of academic databases (PubMed, JSTOR, Scopus) and grey literature from key agencies (WHO, ESA, NASA, UN-COPUOS, COSPAR). We prioritized literature on general practice, bioethics, space medicine, and planetary protection policies. Terrestrial equivalents (pandemic ethics, remote care, biosafety) were included for applicability. Inclusion criteria: relevance to clinical or ethical decision-making in isolation or novel biological hazard environments.Key findings show strong alignment between GPs’ core competencies and the demands of planetary protection protocols. WHO and WMA ethics guidelines emphasize proportionality, psychological support, and least restrictive quarantine—mirroring COSPAR policies requiring containment for astronauts exposed to Martian material. GPs’ pandemic experience reinforces their leadership in risk communication, mental health, and triage. Literature from space agencies anticipates CMO involvement in isolation decisions and contamination mitigation, positioning GPs as de facto bioethical stewards during spaceflight. Terrestrial parallels—Antarctic medicine, COVID-19 response, and biosafety levels—highlight transferable lessons.GPs already possess critical frameworks for managing uncertainty, isolation, and ethical risk. Applying these to spaceflight enhances mission resilience and underscores GPs’ value beyond Earth. However, gaps remain in formal training around planetary bioethics and space operations.This review affirms the relevance of general practice in planetary protection. GPs are well-positioned to integrate clinical care with ethical and environmental safeguards in future Mars missions. We recommend incorporating space-relevant bioethics into primary care training and encouraging interdisciplinary dialogue to prepare for this frontier of care.