Introduction Various studies have linked suicidal behavior, stress, affective disorders, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis resulting from chronic stress. Chronic stress has been shown to cause enlargement of the adrenal glands, altering their function and potentially leading to suicidal behaviors in individuals with depression. This study aimed to compare the histological changes in the adrenal glands of individuals who died by suicide with those who experienced sudden death. Suicide victims are exposed to chronic stress, while individuals with sudden deaths face acute stress related to the act of dying. Methods This analytical study, approved by the Institutional Ethics Committee (IEC), was conducted in the Department of Forensic Medicine and Toxicology at Gandhi Medical College, Bhopal. The study included 100 confirmed cases of suicide, irrespective of gender, aged 15-60 years, with notable autopsy findings, relevant history, no signs of decomposition, and varying survival periods (including immediate deaths within 24 hours). Additionally, 20 controls were selected, involving individuals who died suddenly from causes other than suicide within 24 hours of the incident. Informed consent was obtained using a prescribed proforma from relatives and the police. Histological examination slides of the adrenals were prepared and analyzed. Data were collected and statistically analyzed using GraphPad software and Epi Info 7. Results Capsular hemorrhage was observed in 98% of suicide cases and 40% of controls. Nodulation was present in 48% of suicidal cases and 20% of controls. Zonal extension of zona fasciculata was specific to chronic stress in suicidal cases. In 25% of suicidal cases, a prominent extension of the medulla was noted. Irregular thinning of zona glomerulosa with shrunken cells and increased nuclear density in 88% of cases were considered specific to chronic stress conditions and suicide, not observed in controls. Lipid depletion was observed in all suicidal cases, with diffuse depletion in 47% and focal depletion in 53% of cases. In contrast, 45% of those exposed to the acute stress of dying showed focal depletion, with none exhibiting diffuse depletion. Suicidal cases displayed dilated prominent sinusoids in all three zones and the adrenal medulla (98-99%), absent in controls. Adrenal hemorrhage and necrosis were specific to chronic stress conditions, with 7%, 8%, 32%, and 16% of cases showing hemorrhage in all three zones and adrenal medulla, respectively, and none in controls. Conclusion Histological changes observed in acute stress conditions included focal lipid depletion, capsular hemorrhage, nodular hyperplasia, and hemorrhage and necrosis with edema. However, the proportion and severity of these changes were lower than those observed in the suicidal group, suggesting that these findings may be considered non-specific for differentiating between acute and chronic stress.