Chiral drugs play an important role in modern medicine, but obtaining pure enantiomers from racemic mixtures can pose challenges. When a drug is chiral, only one enantiomer (eutomer) typically exhibits the desired pharmacological activity, while the other (distomer) may be biologically inactive or even toxic. Racemic drug formulations introduce additional health risks, as the body must still process the inactive or detrimental enantiomer. Some distomers have also been linked to teratogenic effects and unwanted side effects. Therefore, developing efficient and scalable methods for separating chiral drugs into their pure enantiomers is critically important for improving patient safety and outcomes. Metal-organic frameworks (MOFs) show promise as novel materials for chiral separation due to their highly tunable structures and interactions. This review summarizes recent advancements in using MOFs for chromatographic and spectroscopic resolution of drug enantiomers. Both the opportunities and limitations of MOF-based separation techniques are discussed. A thorough understanding of these methods could aid the continued development of pure enantiomer formulations and help reduce health risks posed by racemic drug mixtures.