Space exploration’s advancement toward long-duration missions prompts intensified research on physiological effects. Despite adaptive physiological stability in some variables, persistent changes affect genome integrity, immune response, and cognitive function. Our study, utilizing multi-omics data from GeneLab, provides crucial insights investigating muscle atrophy during space mission. Leveraging NASA GeneLab’s data resources, we apply systems biology-based analyses, facilitating comprehensive understanding and enabling meta-analysis. Through transcriptomics, we establish a reference profile of biological processes underlying muscle atrophy, crucial for intervention development. We emphasize the often-overlooked role of glycosylation in muscle atrophy. Our research sheds light on fundamental molecular mechanisms, bridging gaps between space research and terrestrial conditions. This study underscores the importance of interdisciplinary collaboration and data-sharing initiatives like GeneLab in advancing space medicine research.