Osteoarthritis (OA) severity is often exacerbated in individuals with type 2 diabetes mellitus (T2DM), giving rise to a co-morbid condition (OADM) characterized by enhanced metabolic and degenerative alterations. However, the molecular mechanisms underlying this association remain insufficiently understood. In this study, we performed a SWATH-MS-based global proteomic analysis of phenylboronic acid (PBA)-enriched cis-diol–containing glycated/ glycosylated proteins from knee synovial fluid samples of OA and OADM patients. The dataset captures differentially abundant protein signatures associated with metabolic dysregulation, extracellular matrix remodeling, and inflammatory processes in OADM. From a translational perspective, these proteins may have potential relevance as candidate biomarkers for distinguishing OADM from OA and for supporting future investigations into disease stratification and targeted therapeutic approaches.