This article reports on the peroxidase-like catalytic activity of polyoxometalates (POMs) and their potential use as natural peroxidases for developing a simple and efficient colorimetric glucose sensor. Two Keggin-type vanadium-substituted tungstosulfates, [SVW11O40]3− (SVW11) and [SV2W10O40]4− (SV2W10), were tested for their potential as natural enzyme mimetics and exhibited strong peroxidase-like catalytic activity. The catalysis reaction was found to be in accordance with Michaelis-Menten and Lineweaver-Burk kinetics models. Michaelis-Menten constant (Km) and maximum velocity (Vmax) parameters were calculated to be 0.0759 mM and 0.329×10−8 Ms−1 for SVW11, and 0.0543 mM and 2.67×10−8 Ms−1 for SV2W10, respectively, indicating a high catalytic activity and a strong affinity of POMs towards 3,3,5,5-tetramethylbenzidine (TMB). In the case of H2O2, these values were found to be 57.1 mM and 0.325×10−8 mMs−1 for SVW11, and 47.7 mM and 2.72×10−8 mMs−1 for SV2W10. The peroxidase-like catalytic activity of these POMs was used to develop colorimetric glucose sensors as a proof-of-concept model for the POM-based naked-eye detection of biomolecules. The limit of detcetion (LOD) of glucose for SVW11 and SV2W10 was 1.14 μM and 1.24 μM, respectively. Our findings propose broad-ranging potential applications of these novel POMs in biosensing and bioanalytical chemistry.