In this work, we demonstrate the first report on a low-cost, non-enzymatic, label-free electrochemical sensing of alpha-1-acid-glycoprotein (α1GP) biomarker in biofluids using silica embedded carbon nanosheets (SEC) derived from acorn cupules biomass. The SEC/GCE sensor exhibits low detection limit (LOD) of 30 ng/mL (LOD = 3 s/m) which is far below the lowest physiological concentration of α1GP and a wide linear detection range from 100 ng/mL to 10 mg/mL which covers entire clinical concentration range reported for various diseases like cancer, sepsis, etc. The sensing mechanism of the sensor relies on the direct electrooxidation of sialic acid from the α1GP structure which hinder the interfacial electron-transfer process of [Fe (CN)6]3-/4- redox probe at the electrode-electrolyte interface. The sensor exhibits excellent selectivity and stability towards detection of α1GP which is ascribed to the presence of embedded silica nanoparticles on the surface of the carbon nanosheets. The successful determination of α1GP in the simulated blood serum sample with good recovery percentage (i.e., from ∼94.03% to ∼103.50%) proves the feasibility of the sensor towards clinical applications. The overall efficacy of the sensor proves it as a promising low-cost, sustainable, and non-enzymatic platform for a wide variety of bioanalytical applications. © 2021 Elsevier B.V.