Osteoarthritis (OA) and atherosclerosis are chronic degenerative diseases with shared pathophysiological mechanisms. This review explores the link between atherosclerosis and OA progression, focusing on lipid metabolism and adipokines. A systematic review following PRISMA guidelines analyzed 57 studies from PubMed, Elsevier, NCBI, and Google Scholar (2005–2025). Obesity and metabolic disorders, including hypercholesterolemia, contribute significantly to both diseases. Shared mechanisms include chronic inflammation, adipokine dysregulation, and the presence of the Z39Ig protein in affected tissues. Statins, known for their pleiotropic effects, may lower cholesterol and provide chondroprotective benefits. Targeting metabolic factors may improve OA management. Further research on pathophysiological mechanisms and therapeutic interventions could enhance treatment strategies.