Fruits and vegetables are laden with antioxidants and have been used to quench reactive oxygen species. The combination of two or more fruits and vegetables to produce smoothies is expected to yield a synergistic effect that could further improve functionality. This study investigated the antioxidative and blood glucose-lowering potentials of smoothies made from selected fruits and vegetables as well as their effect on the expression of pro-inflammatory genes in streptozotocin-induced diabetic Wistar rats. Standard procedures were used for the in vitro antioxidant determination while pancreas tissue was excised for molecular study. The inclusion of beetroot increased the total phenolic contents by 30-50% while the flavonoid content was increased by more than 3-fold. Similarly, smoothies with beetroot and bitter gourd exhibited stronger free radical scavenging abilities as shown by DPPH (1, 1- diphenyl-2-picrylhydrazyl), ABTS (2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid), Nitric oxide (NO) scavenging ability, metal chelation (Fe2+) and ferric reducing antioxidant properties (FRAP) compared to the sample devoid of the duo. The blood glucose levels of the rats fed the smoothie were significantly lowered with a similar trend in the animals that were administered metformin. The smoothies significantly (p<0.05) reduced the malondialdehyde (MDA) content thus reducing lipid peroxidation in the animals. The endogenous antioxidant enzymes; catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX) in the pancreas were all significantly (p<0.05) increased when the animals were fed smoothies. The expression of pro-inflammatory genes, IL-1β, IL-6 and TNF-α, was down-regulated in the animals fed with smoothies. The findings showed that the smoothies made from the combination have the potential for managing type-2 diabetes mellitus.Graphical