Osthole (OS) is a natural coumarin with a long history of medicinal use in a variety of diseases, such as itch and menstrual disorders. In recent years, OS has been shown to treat inflammation and reduce the expression and activity of NF-κB, although its mechanism of action is still unclear. Overexpression of inflammatory cytokines can have many negative effects in the body, including inducing preterm labor; thus, the modulation of inflammation by OS and its derivatives may be able to delay preterm birth, increasing neonatal survival rates. The objectives of this study were to screen and identify the derivatives of OS with the highest potential for binding capacity to inflammatory mediators NF-κB, TNF-α, and ERK1, and to measure the drug-like properties of these compounds. GLIDE docking in Schrodinger Maestro software was used to calculate docking scores for a variety of semi-synthetic OS derivatives against three proteins involved in inflammation: NF-κB, TNF-α, and ERK1. Schrodinger Qikprop was also used to measure the pharmaceutically relevant properties of the compounds. The protonated demethoxy osthole showed the highest docking of all the proteins tested, while the deprotonated demethoxy osthole consistently had the lowest scores, denoting the importance of pH in the binding activity of this derivative. The lowest docking was at NF-κB, suggesting that this is less likely to be the primary target of OS. All of the screened derivatives showed high drug potential, based on their Qikprop properties. OS and its derivatives showed potential to bind to multiple proteins that regulate the inflammatory response and are prospective candidates for delaying preterm birth.