At the moment, a variety of disasters including climate changes and meteorite fall threaten human society on the earth. So, scientists believe that it is important to explore viable alternative planets in the Solar System to ensure survival of the human civilization. To this end, lots of space exploration missions have been conducted for gaining information about the other parts of the Solar System in the recent years. Astronauts have to confront a lot of challenges in these missions. Long- and short- term spaceflight is associated with physiological and biochemical changes in human body such as changes in body mass, energy balance, water–electrolyte metabolism, calcium and bone metabolism and endocrine system function. These changes which are often in response to adaptation of astronauts’ tissues and systems to environmental changes are affected by microgravity of space, stress, nutrition, changes in sleep cycles, temperature, pressure and humidity. This review describes the physiological and biochemical mechanisms involved in the human body responses to the microgravity and life in space for a long time and possible solutions countermeasures in order to avoid the risk of these changes on the health of the astronauts.