The　use　of　hydrogel-based　bone　adhesives　has　the　potential　to　revolutionize　the　clinical　treatment　of　bone　repairs.　However,　severe　deficiencies　remain　in　current　products,　including　cytotoxicity　concerns,　inappropriate　mechanical　strength,　and　poor　fixation　performance　in　wet　biological　environments.　Inspired　by　the　unique　roles　of　glue　molecules　in　the　robust　mechanical　strength　and　fracture　resistance　of　bone,　a　design　strategy　is　proposed　using　novel　mineral–organic　bone　adhesives　for　strong　water-resistant　fixation　and　guided　bone　tissue　regeneration.　The　system　leveraged　tannic　acid　(TA)　as　a　phenolic　glue　molecule　to　spontaneously　co-assemble　with　silk　fibroin　(SF)　and　hydroxyapatite　(HA)　in　order　to　fabricate　the　inorganic–organic　hybrid　hydrogel　(named　SF@TA@HA).　The　combination　of　the　strong　affinity　between　SF　and　TA　along　with　sacrificial　coordination　bonds　between　TA　and　HA　significantly　improves　the　toughness　and　adhesion　strength　of　the　hydrogel　by　increasing　the　amount　of　energy　dissipation　at　the　nanoscale.　This　in　turn　facilitated　adequate　and　stable　fixation　of　bone　fracture　in　wet　biological　environments.　Furthermore,　SF@TA@HA　promotes　the　regeneration　of　bone　defects　at　an　early　stage　in　vivo.　This　work　presents　a　type　of　bioinspired　bone　adhesive　that　is　able　to　provide　stable　fracture　fixation　and　accelerated　bone　regeneration　during　the　bone　remodeling　process.　©　2019　WILEY-VCH　Verlag　GmbH　&　Co.　KGaA,　Weinheim