Methicillin-resistant Staphylococcus aureus (MRSA) has emerged since the early 1960s. The increasing resistance of pathogens to currently used antibiotics requires the urgent discovery of new antimicrobials effective in combating drug-resistant bacteria. From past to present, medicinal plants are useful to cure human diseases. Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose), commonly found in Phyllanthus species, exerts potentiating effect on β-lactams against MRSA. However, its biological effect may not be fully utilized. Therefore, incorporating microencapsulation technology with the delivery of corilagin would be more effective in utilizing the potential effect on biomedical applications. This work reports the development of a safe micro-particulate system which combined agar with gelatin as wall matrix materials for topical delivery of corilagin in order to eliminate the potential toxicity of the crosslinker formaldehyde. The optimal parameters for microsphere preparation were identified and the particle size of optimal microspheres was 20.11 μm ± 3.58. Antibacterial studies revealed that micro-trapped corilagin (minimum bactericidal concentration, MBC = 0.5 mg/mL) possessed a higher potency against MRSA than free corilagin (MBC = 1 mg/mL). The in vitro skin cytotoxicity showed the safety of the corilagin-loaded microspheres for topical applications, with approximately 90 % of HaCaT cell viability. Our results demonstrated the potential of corilagin-loaded gelatin/agar microspheres for the applicable bio-textile products to treat drug-resistant bacterial infections. Display omitted •We report corilagin-loaded microspheres prepared by a non-toxic gelatin/agar-based system.•Micro-entrapped corilagin showed a stronger antibacterial activity against MRSA than the free drug.•Micro-entrapped corilagin showed lower HaCaT cytotoxicity than the free drug.•Micro-entrapped corilagin with enhanced anti-MRSA activity would be applied to bio-textiles to treat bacterial infections.