20α-hydroxyprogesterone [(20S)-20-hydroxypregn-4-en-3-one, 20α-DHP] is one of the endogenous metabolites of progesterone (Pregn-4-ene-3,20-dione, P4) and a steroid hormone. The literature related to 20α-DHP mainly concentrates on the years from the 1950s to 1970s, and a review of 20α-DHP has not been conducted. In this work, the endogenous and exogenous sources of 20α-DHP are introduced, and methods for determining 20α-DHP in biological samples are described. The biological activities of 20α-DHP are summarized in detail, including the maintenance of pregnancy, endometrial protection, regulation of hormone secretion, ovulation promotion, uterine epithelial cell proliferation, antagonism of breast cancer, and as a diagnostic indicator for psoriasis and polycystic ovarian syndrome. Finally, the pharmacokinetic characteristics of 20α- DHP are briefly introduced to provide a reference for the further development and utilization of 20α-DHP.