Reactive　oxygen　and　nitrogen　species　(RONS)　are　key　signaling　molecules　that　play　an　important　role　in　the　progression　of　inflammatory　diseases.　Although　various　antioxidants　have　RONS　scavenging　properties,　they　are　difficult　to　be　used　to　cope　with　acute　inflammation　which　requires　inflammatory　site-targeting,　effective　anti-inflammatory　activity,　and　low　toxicity.　In　this　work,　we　developed　a　safe　and　effective　nano-antioxidant　ZMF　formed　by　simply　self-assembly　of　natural　plant　protein　zein　and　natural　drug　mangiferin　for　the　synergistic　treatment　of　inflammation-related　acute　liver　injury.　ZMF　could　eliminate　RONS,　inhibit　the　activation　of　macrophages,　and　modulate　the　level　of　inflammatory　cytokines　through　the　synergistic　effects　of　mangiferin　and　zein.　In　addition,　in　the　mouse　models　of　inflammation-related　acute　liver　injury,　ZMF　showed　superior　efficacy　in　reducing　inflammatory　reactions.　Importantly,　the　preliminary　in　vitro　and　in　vivo　experiments　proved　the　good　safety　of　ZMF.　This　study　proved　the　remarkable　anti-inflammatory　activities　of　nanomedicine　self-assembled　by　RONS-eliminating　natural　products,　which　could　provide　a　reference　for　the　green　development　of　efficient　nano-antioxidant　from　natural　products　for　the　treatment　of　inflammation-related　diseases.　©　2023　Elsevier　B.V.