Quercetin, naringenin, and berberine are plant bioactives that can cross the blood-brain barrier and offer neuroprotection. In the present study, we looked into the effect of them on expression of various glucose transporters and key components of brain insulin signalling, namely, insulin receptor substrate 1 (IRS 1), phosphatidyl inositol 3 kinase (PI3K), Akt 1 and low-density lipoprotein receptor-related protein 1 (LRP1) in brain of control, diabetic and bioactive-treated rats by Western blot. Amongst the bioactives tested, quercetin was more potent and restored LRP1 and brain insulin signalling components as well as glucose transporters such as GLUTs 1, 2, 3 and 4 in diabetic animals. On the other hand, berberine and naringenin supplementation to diabetic animals improved brain IRS 1 levels and restored GLUT 1 and GLUT 3 expression without significant effect on PI3K and Akt 1 activation and GLUT 4 levels. From the present study, we conclude that quercetin, naringenin, and berberine can differentially act through insulin-dependent and -independent mechanisms thereby altering glucose homeostasis in the brain during experimental diabetes and bring about the beneficial effect.