The effects of maternal broccoli powder (BP) intake on inflammation and AMPK activation in weaning offspring programmed by maternal undernutrition remain poorly understood. This study aimed to investigate whether maternal BP intake during lactation ameliorates inflammation and affects AMPK phosphorylation in the hypothalamus and liver of weaning offspring subjected to maternal undernutrition. Pregnant rats received either a normal protein (NP, 20% casein) or a low protein (LP, 8% casein) diet. During lactation, dams were provided with either a normal protein diet without or with 0.74% BP (NP/NP or NP/NPBP) or a low protein diet without or with 0.74% BP (LP/LP or LP/LPBP). Blood, liver (left lateral lobular region), and hypothalamic samples (region estimated to include the arcuate nucleus and ventromedial hypothalamus) were collected on postnatal day 21. In the liver, macrophage count, NFκB p65 protein expression, and TNF-α mRNA expression were lower in LP/LPBP than in LP/LP. In the hypothalamus, Iba1 mRNA expression, NFκB p65 protein expression, and TNF-α mRNA expression were reduced in LP/LPBP compared to LP/LP. AMPK phosphorylation was upregulated in both the liver and hypothalamus of LP/LPBP offspring relative to LP/LP. In the liver, mTOR and Akt phosphorylation were downregulated in LP/LPBP compared to LP/LP. Additionally, Dnmt1 levels were lower in LP/LPBP than in LP/LP in the liver, whereas in the hypothalamus, Dnmt1 and Dnmt3a mRNA expression levels were higher in NP/NPBP than in NP/NP. In conclusion, maternal BP intake during lactation decreased inflammation and increased AMPK phosphorylation in the liver and hypothalamus of weaning rats programmed by maternal undernutrition.