Alkaline phosphatase (ALP) is one of the most versatile biomarkers for early detection of several diseases, such as oral carcinomas and periodontitis; therefore, great efforts have been dedicated for developing an ALP biosensor. Multicolor detection of ALP in saliva is ideal for a point-of-care diagnosis; however, this approach is very challenging since spectral responses over wavelengths of several tens of nanometers have thus far remained difficult to achieve. In this work, a colorimetric biosensor for ALP assay has been developed based on ALP affinity to dephosphorylate glucose phosphate into glucose, which has the affinity to deposit Ag nanoshells onto Au nanobipyramids with a multicolor response. This approach provides a blue shift of localized surface plasmon resonance (LSPR) as large as 190 nm corresponding to distinctive color changes, from yellowish brown to red based on the thickness of the formed Ag shell around the Au nanobipyramids. The change in the LSPR has been conducted for highly sensitive quantitative bioassay of ALP with a detectable multicolor change with linear dynamic range of 0.1–20 U/L and low limit of detection (LOD) of 0.085 U/L. Furthermore, the developed multicolor ALP biosensor exhibits high selectivity with high recovery of 98.6% demonstrating  its reliability and suitability for a point-of-care diagnosis. Graphical abstract