Preparedness for nuclear accident responsiveness includes interventions to protect pregnancies against prolonged exposure to radioactive iodine. The aim of this study was to investigate a new design consisting of repeated administration of potassium iodide (KI, 1 mg/kg) for 8 days in late pregnancy gestational day 9–16 (GD9–GD16) in rats. The later-life effects of this early-life iodine thyroid blocking (ITB) strategy were assessed in offspring two months afterbirth. Functional behavioral tests including forced swimming test (FST) and rotarod test (RRT) in rats of both genders showed lower FST performance in KI-treated females and lower RRT performance in KI-treated male pups. This performance decline was associated with metabolic disruptions in cortex involving amino acid metabolism, tyrosine metabolism, as well as docosahexaenoic acid (DHA) lipids and signaling lipids in males and females. Beyond these behavior-associated metabolic changes, a portion of the captured metabolome (17–25%) and lipidome (3.7–7.35%) remained sensitive to in utero KI prophylactic treatment in both cortex and plasma of post-weaning rats, with some gender-related variance. Only part of these disruptions was attributed to lower levels of TSH and T4 (males only). The KI-induced metabolic shifts involved a broad spectrum of functions encompassing metabolic and cell homeostasis and cell signaling functions. Irrespective Regardless of gender and tissues, the predominant effects of KI affected neurotransmitters, amino acid metabolism, and omega-3 DHA metabolism. Taken together, data demonstrated that repeated daily KI administration at 1 mg/kg/day for 8 days during late pregnancy failed to protect the mother-fetus against nuclear accident radiation.