Objectives Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen in nosocomial infections. Since the 1950’s, MRSA has acquired several resistance factors including efflux pumps and drug target modifications. Some studies investigated the anti-MRSA capacity of propolis samples collected in different regions and their immunomodulatory action. The aim of this review is to gather the data published up to August 2022 about propolis action on MRSA strains and its modulatory action on phagocytes. Methods The PubMed database was used looking for articles containing the keywords “propolis”, “immunomodulation”, “MRSA” and the name of each compound. As propolis contains a variety of compounds making it impossible to isolate the major bioactive components, we reviewed the main compounds found in several propolis samples and their mechanisms towards the resistance factors displayed by MRSA. Some perspectives for using propolis-based medications and the formulation of new antimicrobial/immunomodulatory agents are discussed. Key findings Propolis extracts and active compounds exert antibacterial action over MRSA strains acting on resistance factors. Moreover, propolis modulates pro-inflammatory markers in phagocytes. Conclusions Because propolis compounds may act synergistically, it’s crucial to understand how these components interact in order to synthesize standardized formulations and enhance their bioavailability for clinical applications to combat MRSA.