磷酸二酯酶（英语：Phosphodiesterase，简称为PDE）具有水解细胞内第二信使（cAMP,环磷酸腺苷或cGMP,环磷酸鸟苷）的功能，降解细胞内cAMP或cGMP，从而终结这些第二信使所传导的生化作用。

磷酸二酯酶可依以下的特性分类为11型，PDE1至PDE11。

磷酸二酯酶抑制剂是一种抑制磷酸二酯酶活性的药物。例如，西地那非是一种能高选择性地抑制人体内5型磷酸二酯酶（PDE5）活性的磷酸二酯酶抑制剂。

咖啡因同样抑制磷酸二酯酶活性，借此提高细胞内cAMP的浓度，使人比较不想睡眠。

脂肪酶（胆盐依赖性脂酶、胃脂肪酶/舌脂肪酶、胰脂肪酶、溶酶体酸性脂肪酶、激素敏感性脂肪酶、内皮脂肪酶、肝脂肪酶、脂蛋白脂肪酶、单酰基甘油脂肪酶、二酰基甘油脂肪酶）

A phosphodiesterase (PDE) is any enzyme that breaks a phosphodiester bond. Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases (which all break the phosphodiester backbone of DNA or RNA), as well as numerous less-well-characterized small-molecule phosphodiesterases.