Finger millet (FM) and kodo millet (KM) are known for their multiple health benefits. Several studies have indicated the antioxidant and hypoglycemic potential of polyphenol rich extracts (PREs) from them. However, the protective roles of PREs from these millets in overcoming high-fat diet (HFD)-induced obesity have not yet been investigated. This study aimed to identify the polyphenols in FM-PREs and KM-PREs using HPLC-DAD/ESI-MS, and to evaluate the role of PREs in mitigating lipopolysaccharide induced inflammation in murine macrophage cells and in the reduction of HFD-induced metabolic complications using male Swiss albino mice. The results suggested that KM-PRE had higher polyphenol content than FM-PRE, of which taxifolin (98%) and catechin (86.6%) were the major fractions respectively. FM-PRE and KM-PRE prevented obesity, however, KM-PRE was more profound in preventing weight gain, adipose tissue hypertrophy, hepatic steatosis, and systemic inflammation than FM-PRE. This study suggests that FM-PRE and KM-PRE could be exploited for developing functional foods or nutraceuticals against obesity and comorbidities.