The hyaline cartilage is an avascular, aneural and alymphatic tissue with a limited ability to repair itself. When the cartilage is exposed to some kind of injury, it usually triggers osteoarthritis (OA), a prevalent and degenerative joint disease closely related to aging. OA is both complex and multifactorial, and is the most common form of arthritis, being positioned as a major cause of pain and dysfunction in the world. In addition, high OA prevalence can greatly affect work capacity, making this disease a significant social problem, therefore, its prevention and treatment becomes a priority. At this time, there are numerous therapeutic strategies available to improve hyaline cartilage repair by using chondrocytes or mesenchymal cells, but neither is effective enough to generate functional and durable tissue reparation over time. In OA, chondrocytes have an aberrant gene expression and phenotype, resulting in a loss of balance between anabolic and catabolic processes. Environmental influences such as radiation, infection, smoking, nutrients, toxins and stress can affect gene expression patterns, which may constitute risk factors for various chronic and degenerative diseases, such as OA. In addition, considerable evidence shows that epigenetic mechanisms play an important role in OA chondrogenesis and pathogenesis. Natural plant-derived products such as polyphenols, which are secondary metabolites considered to have potential activity to block inflammation in several degenerative diseases, can stimulate epigenetic modifications, and may provide new therapeutic targets and cost-effective treatments. This review aims to present various polyphenolbased therapies currently used for the treatment of several progressive diseases, including OA.