Progesterone, a steroid hormone secreted by the ovaries, plays an indispensable role in reproductive physiology and obstetric care. Its functions span from maintaining uterine quiescence to immunomodulation, facilitating successful implantation and pregnancy maintenance. Progesterone acts by inhibiting prostaglandin synthesis, and reducing myometrial contractions. Additionally, it fosters endometrial changes conducive to embryo implantation by enhancing vascularity and oxygen supply. The immunomodulatory properties of progesterone involve a shift from Th1 to Th2 immune responses, crucial for fetal tolerance. In assisted reproductive technology (ART), progesterone supplementation is critical due to the potential luteal phase defects caused by medical interventions. Studies have demonstrated the efficacy of natural micronized progesterone (NMP) in various forms, including oral, vaginal, and intramuscular (IM) administration. Oral NMP has shown comparable efficacy to IM forms in raising serum progesterone levels, thereby supporting luteal function and extending pregnancy duration. Comparative studies on different progesterone formulations indicate that oral sustained-release NMP (SR) is effective in maintaining adequate luteal phase progesterone levels, thus supporting pregnancy. Clinical evidence highlights the beneficial effects of progesterone in preventing recurrent miscarriages and managing threatened abortions. Progesterone's role extends to reducing pro-inflammatory cytokines like IL-6 and TNF-α while increasing anti-inflammatory cytokines such as IL-10, thereby promoting a favorable environment for pregnancy continuation. In summary, progesterone's multifaceted actions, including hormonal and non-hormonal mechanisms, underscore its essential role in obstetrics. Its application in managing luteal phase defects, recurrent miscarriages, and threatened preterm births demonstrates its critical impact on optimizing pregnancy outcomes. The distinction between natural progesterone and synthetic progestins is crucial, given their varying safety profiles and pharmacological effects. Large population studies have demonstrated safety of natural progesterone in pregnancy however, concern remains with synthetic progestin. Continued research and clinical application of progesterone will enhance its utility in reproductive medicine, providing better outcomes for patients experiencing reproductive challenges.