Major depressive disorder and anxiety disorders are two mental diseases that are treated with amitriptyline (AMT). AMT treatments induced liver, heart and testes toxicity; As a result, the purpose of this study was to determine the preventative and therapeutic role of damiana (Dam) as adjuvant herbal therapy against AMT induced heart injury in rats. Six groups of 36 rats (male albino) were randomly assigned; first one is control, second is Dam, third was AMT, fourth was Dam+AMT, fifth was AMT+Dam and sixth was AMT self-healing. A significant elevation in creatinine, urea, sodium (Na+), Chloride (Cl+), renal injury, DNA damage and apoptosis in treatment rats with amitriptyline and self-healing group as related to control and damiana groups. Conversely; potassium (K+) and calcium (Ca++) were a significant decrease in AMT and self-healing groups as compared with control. Treatment of AMT with Dam (Co and Post) revealed a modulation and improvement of renal toxicity with best result in co- treatments than post treatments. As a result, AMT treatments encouraged changes in kidney functions and structure and the post-treatments of AMT with dam modulates these alterations.