The study of cell membrane structures under microgravity is crucial for understanding the inherent physiological and adaptive mechanisms relevant to overcoming challenges in human space travel and gaining deeper insight into the membrane-protein interactions at reduced gravity. However, the membrane dynamics under microgravity conditions is not unraveled yet. Moreover, the complexity of cells poses significant challenges when investigating the effects of microgravity on individual components, including cell membranes. Giant Unilamellar Vesicles (GUVs) serve as valuable cell-mimicking models and act as artificial cells, providing insights into the biophysics of membrane architecture. Herein, we have elucidated the membrane dynamics of artificial cells under simulated microgravity conditions. GUVs were synthesized in the size range of 20 ± 2.1 μm and their morphological changes were examined under simulated microgravity conditions using a random positioning machine. We observed that the well-defined spherical GUVs were transfigured and deformed into elongated structures under microgravity conditions. The membrane fluidity of GUVs increased sevenfold under microgravity conditions compared to GUVs under normal gravity conditions at 48 h. It is also noted that there is a reduction in the membrane microviscosity. The study sheds light on the membrane mechanics under microgravity conditions and contributes valuable insights to the broader understanding of membrane responses to microgravity and its implications for space exploration and biomedical applications.