Antimicrobial resistance is an issue of global relevance for the treatment of chronic wound infections. In this study, nano-in-micro hydrogels (microbeads) of chitosan and κ-carrageenan (CCMBs) containing curcumin-loaded rhamnosomes (Cur-R) were developed. The potential of Cur-R-CCMBs for improving the antibacterial activity and sustained release of curcumin was evaluated. Curcumin-loaded rhamnosomes (rhamnolipids functionalized liposomes) had a mean particle size of 116±7nm and a surface-charge of -24.5±9.4mV. The encapsulation efficiency of curcumin increased from 42.83%±0.69% in Cur-R to 95.24%±3.61% respectively after their embedding in CCMBs. SEM revealed smooth surface morphology of Cur-R-CCMBs. FTIR spectroscopy confirmed the presence of weak electrostatic and hydrophobic interactions among curcumin, rhamnosomes, and microbeads. Cur-R-CCMBs had demonstrated significant antibacterial activity against multi-drug resistant chronic wound pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. Cur-R-CCMBs also exhibited significantly higher anti-oxidant (76.85%±2.12%) and anti-inflammatory activity (91.94%±0.41%) as well as hemocompatibility (4.024%±0.59%) as compared to pristine microbeads. In vivo infection model of mice revealed significant reduction in the viable bacterial count of S. aureus (∼2.5 log CFU/mL) and P. aeruginosa (∼2 log CFU/mL) for Cur-R-CCMBs after 5days. Therefore, nano-in-micro hydrogels can improve the overall efficacy of hydrophobic antimicrobials to develop effective alternative-therapeutics against resistant-pathogens associated with chronic wound infections.