The adrenal gland is the most important steroidogenic tissue in the human body and essential for survival and plays a tremendous number of vital activities in the human body. The present research aimed to evaluate the hazardous effects of Dexamethasone (DM) and alprazolam (ALZ) on adrenal tissue of male rats exposed to daily administration of (DM) and (ALZ) for 2 weeks followed by withdrawal period for another 2 weeks, Through evaluation of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Alkaline Phosphatase (ALP) activities and Albumin, Total Protein, Total Bilirubin, Urea, Creatinine, Sodium (Na), Potassium (K) concentrations. Levels of serum Cortisol, Aldosterone, C-Reactive Protein (CRP), Interleukin-2 (IL-2), and Interleukin-6 (IL-6), were also determined. Administration of DM and ALZ daily for 2 weeks induced a significant increase in 1) Serum ALT, AST, and ALP activities, in addition to Total Bilirubin, Urea, Creatinine and Na concentrations. 2) Serum Cortisol, Aldosterone, CRP, IL-2, IL-6. On contrast, it exhibited a significant decrease in serum K, albumin and Total Protein. Withdrawal of DM and ALZ gradually for another 2 weeks returned all the biochemical parameters to be near the normal values.