The aim of this work was to fabricate polylactide-based hollow microspheres to act as slow-release antimicrobial carriers with prolonged antibacterial activity for controlled release applications and also to sharpen our understanding behind its slow release. Hollow particles were fabricated via water/oil/water (w/o/w) double-emulsion method by using hot water to accelerate solvent evaporation rate in order to make hollow core whereas non-hollow (solid) microspheres were formed via simple oil/water (o/w) emulsion method. Interestingly, in vitro release of hydrophilic antibacterial from solid microspheres (hydrophobic) were extremely slow due to strong association between antibacterial and polymer (polylactide) matrix via H-bonding, investigated by Raman microscopy and DSC study. The release rate increases significantly (> 4 times) in the case of hollow particles. The release kinetics study revealed that both hollow and solid particles predominantly followed diffusion-controlled process rather than a degradation pathway. These hollow microspheres demonstrate great promise as antibacterial agents against both gram-negative and gram-positive bacteria over a period of 30 days at 37 A degrees C. The antibacterial effect of these particles was also evaluated on a food model (watermelon juice) and a significant reduction in bacterial growth was observed especially in the case of hollow microparticles. Hence, PLA-based hollow microspheres can be proposed as slow-release antimicrobial carriers for drug delivery or active packaging applications due to its ease of preparation and simplicity.