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Child maltreatment is a widespread global issue involving any form of harm or neglect by a parent or caregiver, leading to various forms of physical or emotional damage, with approximately 150 million affected children globally. This study discusses the potential mechanism of the hypothalamic-pituitary-adrenal axis dysfunction and cortisol hormone changes in linking child maltreatment to mental health disorders. It also discusses supportive strategies to prevent mental diseases and counteract the biological embedding of these conditions, emphasizing the need for comprehensive interventions to address the long-term impact of child maltreatment on mental health. Articles were selected using established methods previously described. Key information was obtained from scientific articles published during the past 20 years, including original studies, systematic reviews, and meta-analyses. Articles search was performed using top academic search engines. While research on hypothalamic-pituitary-adrenal axis response to stress in maltreated children is ongoing and far from conclusive, its impact and implications for physiological functioning and the predisposition to psychopathology are significant. Childhood maltreatment increases the risk of psychiatric illnesses, severity of diseases, and poor treatment responses. Childhood maltreatment manifests as disruptions to hypothalamic-pituitary-adrenal axis functioning, with the extent varying based on factors, such as the age of onset, parental responsiveness, and the type and characteristics of maltreatment. The complex interplay of these factors contributes to the diversity of hypothalamic-pituitary-adrenal axis responses to stress in maltreated children, creating a spectrum of physiological functioning and vulnerability to psychopathology., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)