Colonization of the Moon and other planets is an aspiration of NASA and may yield important benefits for our civilization. The feasibility of such endeavors depends on both innovative engineering concepts and successful adaptation of life forms that exist on Earth to inhospitable environs. In such missions plants will play a vital role as life support systems, supplying astronauts with food, oxygen, carbon dioxide recycling, and psychological well-being benefits. Therefore, understanding the adaptability of plants to harsher environments, including different gravitational forces and growth on extraterrestrial soils will be required. In this study, we investigate the potential of Raman spectroscopy (RS), a modern analytical technique, in a non-invasive and non-destructive assessment of changes in the biochemistry of plants exposed to zero gravity on the International Space Station and during growth on lunar regolith simulants on Earth. We report that RS can sense changes in plant carotenoids, pectin, cellulose, and phenolics, which in turn, could be used to gauge the degree of plant stress to the new environments. Our findings also demonstrate that RS can monitor the efficiency of soil supplements that can be used to mitigate nutrient-free regolith media. We conclude that RS can serve as a highly efficient, fast, and label-free approach for monitoring plant health in exotic environments.