Exposure to early life stress (ELS) leads to an increased risk for psychopathology and emotional dysregulation. Knowledge on underlying mechanisms and interventions are lacking. We previously found that early methyldonor supplementation protects against ELS-induced cognitive deficits, mediated partly by HPA-axis modulation. Methyldonors are essential micronutrients and key for methyl group generation for methylation of DNA and histones. Our study aimed to understand how ELS and early micronutrient intervention affect (i) HPA-axis responsivity and anxiety/depressive-like behavior, and (ii) hypothalamic epigenetic signature. C57Bl/6 mice were subjected to ELS by the limited and nesting bedding (LNB) paradigm from postnatal day (P)2-9, during which the dam were fed a control or methyldonor-supplemented diet. At P40 the animals underwent acute restraint stress followed by a battery behavioural tests after which epigenetic changes were analysed at P60 by genome wide DNA methylation array. We demonstrated that (i) ELS exposure followed by acute stress leads to anxiogenic behaviour and impaired self-care, (ii) early methyldonor supplementation prevents ELS-induced anxiogenic behaviour and reverses impaired self-care behaviour, without affecting depressive-like behaviour, (iii) both ELS and early methyldonor supplementation do not affect the basal and acute stress-induced corticosterone levels. Moreover, we demonstrated that (iv) acute stress leads to a DNA methylation signature in the hypothalamus, (v) early micronutrient diet has a long-term impact on the hypothalamic methylation profile, (vi) that both of these signatures are altered when exposed to ELS. In summary, our study showed that early nutritional interventions counteract emotional dysregulation during adolescence potentially mediated via hypothalamic DNA methylation alterations.