Osteoarthritis (OA) is a long-term degenerative joint condition that progressively impairs movement and reduces quality of life, especially among older and obese individuals. Existing treatments, such as oral nonsteroidal anti-inflammatory drugs, mainly provide symptomatic relief but are often associated with systemic side effects and insufficient drug concentration at the site of action. This has created a need for more targeted and safer delivery approaches. In recent years, transethosomes have gained attention as a promising transdermal drug delivery system. These vesicular carriers, composed of phospholipids, ethanol, and surfactants, are designed to be highly flexible and capable of penetrating the skin barrier effectively. Their structure allows improved drug loading, enhanced permeation, and sustained release, making them suitable for delivering a wide range of therapeutic agents directly to affected tissues. However, certain challenges, including formulation instability, drug leakage, and the potential for skin irritation due to ethanol content, still need careful consideration. Emerging strategies such as dry transethosomal systems and incorporation into hydrogels are showing encouraging progress in addressing these limitations. Overall, transethosomes offer a practical and evolving solution for localized osteoarthritis treatment, with the potential to improve therapeutic outcomes and patient adherence as research advances.