Phosphodiesterase 4 (PDE4) inhibitors are effective therapeutic agents for various inflammatory diseases, including chronic obstructive pulmonary disease (COPD), psoriatic arthritis, and atopic dermatitis. These inhibitors increase cyclic adenosine monophosphate (cAMP) levels, regulating genes and proteins to exert multiple effects. While they have shown promise in treating inflammatory conditions, their use is often limited by adverse reactions such as nausea, vomiting, and gastrointestinal disturbances. This review discusses the clinical applications and anti-inflammatory mechanisms of PDE4 inhibitors, their potential protective effects on vascular diseases, and strategies to mitigate adverse reactions. The review highlights the need for further research to explore the therapeutic potential and clinical applications of PDE4 inhibitors in vascular diseases.Phosphodiesterase 4 (PDE4) inhibitors are effective therapeutic agents for various inflammatory diseases, including chronic obstructive pulmonary disease (COPD), psoriatic arthritis, and atopic dermatitis. These inhibitors increase cyclic adenosine monophosphate (cAMP) levels, regulating genes and proteins to exert multiple effects. While they have shown promise in treating inflammatory conditions, their use is often limited by adverse reactions such as nausea, vomiting, and gastrointestinal disturbances. This review discusses the clinical applications and anti-inflammatory mechanisms of PDE4 inhibitors, their potential protective effects on vascular diseases, and strategies to mitigate adverse reactions. The review highlights the need for further research to explore the therapeutic potential and clinical applications of PDE4 inhibitors in vascular diseases.