In　this　work,　we　have　synthesized　Cu2+-modified　carbon　nitride　nanosheets　(Cu2+-C3N4)　as　peroxidase　mimic　catalytic　substance,　which　is　more　active　than　the　horseradish　peroxidase　enzyme　in　extreme　environments.　Gold　nanobipyramid　(Au　NBP)　is　a　good　chromogenic　substrate　for　multicolor　display　because　the　longitudinal　plasmon　bands　of　AuNRs　can　be　easily　tuned　by　adjusting　their　aspect　ratios　and　used　as　an　excellent　indicator　for　colorimetric　detection　of　immunoassays.　The　generation　of　TMB2+　from　sandwich　complex　(peroxidase-like　catalysis)　efficiently　etches　Au　NPBs　to　produce　multicolor　variations　from　brown　to　olive,　green,　blue,　purple,　purple,　red,　pink,　and　colorless　in　presence　of　varied　concentrations　of　neuron　specific　enolase　(NSE).　The　experimental　results　show　that　the　colorimetric　detection　ranging　from　312.5　to　20,000　pM　with　a　detection　limit　of　92.8　pM,　which　is　higher　than　other　multicolor　based　sensors.　The　Cu2+-C3N4　nanosheets　and　Au　NBPs　based　colorimetric　visual　(naked　eye)　semi-quantitative　method　as　a　potential　platform　towards　the　detection　of　important　biomolecules　in　clinical　and　therapeutic　applications.　The　proposed　method　is　simple,　low-cost　and　enzyme-free　to　detect　NSE　for　the　first　time.　©　2018　Elsevier　B.V.