The present study investigated the antioxidant potential of guar gum macroparticles (GGMs), vanadium oxide sulphate (VS) encapsulated guar gum macroparticles (GVMs), guar gum nanoparticles (GGNs), VS encapsulated guar gum nanoparticles (GVNs) and VS. GGNs and GVNs prepared by nanoprecipitation were characterized by SEM (scanning electron microscopy), TEM (transmission electron microscopy) and particle size analysis to confirm the nanostructure of the particles. Particle size analysis revealed that GVNs possess a size of 239 nm, about 148 nm larger than that of GGNs. TEM imaging and EDAX data also confirmed the formation of fine spherical nanoparticles with vanadium incorporation. In addition the larger size of GVNs also confirmed the vanadium incorporation. MTT assay showed that concentrations up to 100 nM of GVNs for 24 h exposure did not induce significant toxicity when VS was toxic (16%) at 100 nM. Various in vitro antioxidant assays (total reducing power, total antioxidant capacity, DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid), hydroxyl radical and superoxide anion radical scavenging assays) revealed significantly high antioxidant potential of GVNs compared to GGNs, VS, GGMs and GVMs. The IC50 of GVNs was 23.21 ± 2.1 μg mL(-1), 33.0 ± 2.93 μg mL(-1), 21 ± 1.98 μg mL(-1) and 22.79 ± 2.12 μg mL(-1) for DPPH, ABTS, hydroxyl, superoxide anion scavenging activity assays respectively. The cell line based assay also proved that the GVN was more effective in reactive oxygen species (ROS) scavenging than VS against tertiary butyl hydrogen peroxide (TBHP) induced oxidative stress in H9c2 cell lines. The overall results indicated that vanadium in combination with nano guar gum exhibits significantly high antioxidant potential.