Pirfenidone and nintedanib are antifibrotic drugs used to treat idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). Both drugs have shown efficacy in slowing disease progression but also cause various side effects, including gastrointestinal symptoms, photosensitivity, and skin rashes. The review evaluates the effectiveness and safety of these drugs in different ILD conditions, including IPF, post-COVID-19 fibrosis, systemic sclerosis-associated ILD (SSc-ILD), rheumatoid arthritis-associated ILD (RA-ILD), idiopathic inflammatory myopathies (IIM)-ILD, and stage IV sarcoidosis. The study highlights that both drugs reduce the decline in forced vital capacity (FVC), a key indicator of lung function, and improve survival rates. However, their use is associated with side effects that may necessitate dose adjustments or discontinuation. Nintedanib is generally better tolerated than pirfenidone, but both drugs have similar efficacy in slowing disease progression. The review also discusses the cost-effectiveness of these drugs and the need for further research to optimize their use in ILD patients. The findings suggest that both drugs are valuable in managing fibrosing ILDs, but their use should be individualized based on patient tolerance and disease characteristics. The review emphasizes the importance of monitoring adverse effects and considering combination therapies to improve outcomes. Overall, pirfenidone and nintedanib are important treatment options for ILD patients, but further studies are needed to fully understand their role in different disease settings.Pirfenidone and nintedanib are antifibrotic drugs used to treat idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases (ILDs). Both drugs have shown efficacy in slowing disease progression but also cause various side effects, including gastrointestinal symptoms, photosensitivity, and skin rashes. The review evaluates the effectiveness and safety of these drugs in different ILD conditions, including IPF, post-COVID-19 fibrosis, systemic sclerosis-associated ILD (SSc-ILD), rheumatoid arthritis-associated ILD (RA-ILD), idiopathic inflammatory myopathies (IIM)-ILD, and stage IV sarcoidosis. The study highlights that both drugs reduce the decline in forced vital capacity (FVC), a key indicator of lung function, and improve survival rates. However, their use is associated with side effects that may necessitate dose adjustments or discontinuation. Nintedanib is generally better tolerated than pirfenidone, but both drugs have similar efficacy in slowing disease progression. The review also discusses the cost-effectiveness of these drugs and the need for further research to optimize their use in ILD patients. The findings suggest that both drugs are valuable in managing fibrosing ILDs, but their use should be individualized based on patient tolerance and disease characteristics. The review emphasizes the importance of monitoring adverse effects and considering combination therapies to improve outcomes. Overall, pirfenidone and nintedanib are important treatment options for ILD patients, but further studies are needed to fully understand their role in different disease settings.