During the space travel mission, astronauts' physiological and psychological behavior will alter, and they will start consuming terrestrial drug products. However, factors such as microgravity, radiation exposure, temperature, humidity, strong vibrations, space debris, and other issues encountered, the drug product undergo instability This instability combined with physiological changes will affect the shelf life and diminish the pharmacokinetic and pharmacodynamic profile of the drug product. Consequently, the physicochemical changes will produce a toxic degradation product and a lesser potency dosage form which may result in reduced or no therapeutic action, so the astronaut consumes an additional dose to remain healthy. On long-duration missions like Mars, the drug product cannot be replaced, and the astronaut may relay on the available medications. Sometimes, radiation-induced impurities in the drug product will cause severe problems for the astronaut. So, this review article highlights the current state of various space-related factors affecting the drug product and provides a comprehensive summary of the physiological changes which primarly focus on absorption, distribution, metabolism, and excretion (ADME). Along with that, we insist some of the strategies like novel formulations, space medicine manufacturing from plants, and 3D printed medicine for astronauts in longer-duration missions. Such developments are anticipated to significantly contribute to new developments with applications in both human space exploration and on terrestrial healthcare.