<p>Propolis is widely known for its therapeutic properties, including antimicrobial properties closely linked to its complex and variable phytochemical composition, which differs according to botanical and geographical origin—green, red, brown, and yellow types. Its antimicrobial activity is particularly effective against Gram-positive bacteria, fungi, and certain viruses. The underlying mechanisms involve apoptosis induction, inhibition of virulence factors, and suppression of protein synthesis. Propolis has low oral bioavailability, which may impair its antimicrobial potential. Nanoparticles have been widely developed to improve the pharmacokinetic drawbacks of active compounds, and for propolis, represent an important tool resulting in higher antimicrobial activity. However, the development of nanostructured delivery systems to enhance propolis delivery remains limited. Nanoparticle-based formulations have emerged as promising strategies to overcome these pharmacokinetic limitations, improving stability, absorption, and antimicrobial efficacy. This review discusses the antimicrobial mechanisms of propolis and highlights advances in nanostructured systems developed to optimize its oral delivery.</p> Graphical Abstract <p></p>