Space exploration introduces unique health challenges for astronauts, including musculoskeletal degradation, immune dysregulation, oxidative stress, and cardiovascular alterations, primarily due to microgravity and space radiation. Conventional solutions like synthetic drugs face limitations such as side effects and storage constraints during long missions. Phytomedicine, derived from plant bioactive compounds, offers a promising alternative to address these challenges through multitargeted therapeutic actions. However, most evidence on these plant-based interventions comes from terrestrial preclinical and clinical studies, with only sparse data from microgravity or space analog environments, so their relevance to spaceflight must be interpreted cautiously. This review article explores the potential integration of phytomedicine into space health protocols to enhance astronaut well-being and mission success. The review synthesized findings from diverse studies on the health effects of microgravity and the therapeutic potential of phytomedicines. Relevant literature was sourced from scientific databases notably Scopus and Web of Science (2012-2025). Key bioactive compounds and their mechanisms were evaluated in relation to space-relevant conditions and their feasibility for use in space environments, while noting that the vast majority of included studies were conducted under terrestrial conditions. The findings were synthesized to propose phytomedicine as a viable addition to astronaut healthcare protocols. Phytomedicines demonstrate significant potential in mitigating space-induced health issues. Resveratrol and curcumin support bone and muscle health, flavonoids and sterols enhance cardiovascular resilience, and compounds like Ginkgo biloba and ashwagandha provide neuroprotective and adaptogenic benefits. Phytomedicines' advantages include multitargeted actions, compact storage, and alignment with sustainable exploration goals, such as bioregenerative cultivation systems. These benefits, however, are inferred largely from Earth-based models and patient populations, and should therefore be viewed as preliminary indicators rather than space-validated countermeasures. Challenges like stability, integration with protocols, and standardization were also identified. Phytomedicine represents a transformative approach to astronaut healthcare, offering holistic and sustainable solutions to counteract the adverse effects of space travel including musculoskeletal loss, immune dysregulation, oxidative stress, and neurocognitive strain. While promising, its integration requires further research, development of space-specific formulations, and interdisciplinary collaboration. Addressing these gaps could revolutionize space medicine and support the success of long-duration space missions.
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