Chronic　wounds　with　multidrug-resistant　bacterial　infections　substantially　delay　the　healing　procedure　and　correlate　with　clinical　implications,　including　pain　increase　and　quality　of　life　reduction.　Therapeutic　approaches　that　could　kill　bacteria　and　promote　wound　healing　are　highly　desired　for　the　treatment　of　chronic　nonhealing　wounds.　Metal　oxide-based　nanoagents　show　increasing　potential　as　a　burgeoning　type　of　antibiotic　for　multidrug-resistant　bacterial　infections.　In　this　study,　we　developed　two　kinds　of　Fe-　and　Ca-incorporating　mesoporous　silica　nanoparticles　(FeCaSi)　via　a　simple　and　practicable　strategy.　They　can　be　applied　for　the　administration　of　bacterial　infection　and　wound　healing.　The　antibacterial　properties　of　FeCaSi　nanoagents　include　bacterial　cell　wall　capturing　and　subsequent　reactive　oxygen　species　(ROS)-producing　activity;　besides,　the　killing　capacity　can　be　tailored　by　adjusting　the　ratio　between　Fe　and　Ca　to　be　4:3　(FeCaSi4:3),　which　is　optimal　for　the　eradication　of　drug-resistant　Escherichia　coli　and　Staphylococcus　aureus　infection.　Furthermore,　treatment　with　FeCaSi4:3　could　reduce　the　bacteria　in　the　skin,　promote　collagen　deposition,　and　accelerate　the　healing　of　bacterial-infected　wounds　in　mice.　Our　study　provided　a　simple　but　powerful　way　to　engineer　metal　oxide　mesoporous　nanoparticles　for　antibacterial　therapy.　©　2024　American　Chemical　Society.