Fibromyalgia (FM), the most common cause of chronic musculoskeletal pain in the general public, lacks advanced therapeutic methodology and detailed bioinformation. However, acting as a newly developed and important transition metal carbide or carbonitride, the MoC nanozyme has provided a novel iatrotechnique with excellent bioactivity in a cell/animal model, which also exhibits potential prospects for future clinical applications. In addition, high-content and high-throughput integrated metabolomics (including aqueous metabolomics, lipidomics, and desorption electrospray ionization-mass spectrometry imaging) also specializes in qualitative and quantitative analysis of metabolic shifts at the molecular level. In this work, the FM-alleviation effect of MoC nanozyme was investigated through integrated metabolomics in a mouse model. An advanced platform combining gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry and bioinformatics was utilized to study the variation in the mouse metabolome and lipidome. The results revealed that MoC treatment could effectively enhance energy metabolism-related biological events impaired by FM, leading to homeostasis of oxidative stress and energy metabolism toward the control levels. During this process, MoC facilitated the elimination of ROS in plasma and cells and the rehabilitation of mice from oxidative stress and mitochondrial dysfunction. It was believed that such an integrated metabolomics study on the FM-alleviation effect of MoC nanozyme could provide another excellent alternative to traditional MoC-based research with numerous pieces of bioinformation, further supporting research area innovation, material modification, and clinical application.