This study aims to analyze the influence of the water-based extract from Khat leaves, a plant frequently chewed in the Arabian Peninsula and the Horn of Africa, on the health of various vital organs. Thirty (30) albino female rats were randomized into two groups: a control group and a treatment group. The treatment group provided 1 mL of a 700 mg/kg aqueous Khat extract daily for four weeks. Khat-treated rats revealed greater malondialdehyde (MDA) levels, indicating increased oxidative stress. At the same time, their antioxidant enzymes—glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)—declined dramatically. This shows that Khat affects the body's balance between oxidative stress and antioxidant defenses. This suggests an imbalance in the oxidative state, accompanied by heightened oxidative damage. Cytokine profiling indicated a considerable decline in the anti-inflammatory cytokine interleukin-4 (IL-4), alongside a rise in the proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta 1 (TGF-β1). The findings suggested that cardiac enzymes such as troponin, creatine kinase (CK), creatine phosphokinase (CPK), and aspartate aminotransferase (AST) were considerably elevated in the Khat treatment cohort. The hormonal testing demonstrated a considerable spike in follicle-stimulating hormone (FSH), luteinizing hormone (LH), and serum testosterone, accompanying a marked fall in estrogen levels. Histological investigations indicated significant abnormalities in the tissue architecture of the heart, brain, and ovaries in the Khat-treated patients. The findings suggest that protracted intake of Khat as a masticatory material may adversely influence the body's essential organs.