Staphylococcus aureus infection is one of the common clinical infectious diseases. Its clinical treatment encounters significant challenges. Peroxisome proliferator-activated receptor γ (PPARγ), as a member of the nuclear receptor family, has multiple mechanisms in regulating inflammatory response, immune cell function, and skin barrier repair, and plays a key role in Staphylococcus aureus infection. PPARγ can inhibit excessive inflammatory response, reconstruct immune response, and promote epidermal regeneration, thus is expected to be a new target for the treatment of Staphylococcus aureus infection. This review systematically summarizes the molecular network of PPARγ in inflammation regulation, immunoregulation, and barrier repair, aiming to provide theoretical basis for the development of targeted therapy strategies.