This review explores the multifaceted relationship between osteoarthritis (OA) and various systemic diseases, highlighting the extensive impact of OA on patients' health. OA, a chronic degenerative joint disease, affects over 500 million people worldwide, causing pain and disability. Beyond its direct impact on joint functionality, OA is associated with a range of comorbidities, including osteoporosis, sarcopenia, cardiovascular diseases, diabetes mellitus, neurological disorders, mental health issues, and even cancer. Shared inflammatory processes, genetic factors, and lifestyle elements link OA to these conditions. The review emphasizes the need for a holistic approach to managing OA and its complications, including early screening, timely interventions, and comprehensive patient care to improve overall health and reduce the burden of associated diseases. Understanding the intricate mechanisms underlying the relationships between OA and systemic diseases is crucial for developing more effective therapeutic strategies.This review explores the multifaceted relationship between osteoarthritis (OA) and various systemic diseases, highlighting the extensive impact of OA on patients' health. OA, a chronic degenerative joint disease, affects over 500 million people worldwide, causing pain and disability. Beyond its direct impact on joint functionality, OA is associated with a range of comorbidities, including osteoporosis, sarcopenia, cardiovascular diseases, diabetes mellitus, neurological disorders, mental health issues, and even cancer. Shared inflammatory processes, genetic factors, and lifestyle elements link OA to these conditions. The review emphasizes the need for a holistic approach to managing OA and its complications, including early screening, timely interventions, and comprehensive patient care to improve overall health and reduce the burden of associated diseases. Understanding the intricate mechanisms underlying the relationships between OA and systemic diseases is crucial for developing more effective therapeutic strategies.