Aim <p>This study aimed to demonstrate the histological changes in the submandibular salivary glands (SMSGs) and kidneys induced by Amiodarone in albino rats, and to assess the potential therapeutic effects of bone marrow stem cells conditioned medium (BMSCs-CM).</p> Methods <p>Thirty adult male Sprague Dawley Albino rats (180–230&#xa0;g, aged 3–4 months, were arbitrarily divided into three equal groups. Group I (control): received a balanced diet and water for six days without medication. Group II (Amiodarone Group): was administered Amiodarone intraperitoneally at 50 mg/kg/day for six days. Group III (Conditioned media (CM) Group): received the same treatment as Group II, followed by intravenous injection of 1 ml BMSCs-CM for four consecutive days. At the end of the experiment, all rats were euthanized, and salivary gland and kidney samples were collected for histological analysis using hematoxylin and eosin (H&amp;E), Masson's trichrome, and caspase 3 staining. ELISA was used to quantify tissue levels of malondialdehyde (MDA) and catalase (CAT).</p> Results <p>Histologically, Group III's findings were almost resembled to those of Group I, with normal SMSG and kidney features. Group III salivary glands showed lower MDA levels (17.47 ± 0.58) compared to the Amiodarone treated samples (24.17 ± 1.72) and greater CAT levels (60 ± 5.06) compared to the Amiodarone group (35.33 ± 2.73). Administration of CM significantly increased CAT (23.66 ± 1.36) and decreased MDA levels in kidney samples (5.53 ± 0.31) as compared to the Amiodarone group.</p> Conclusions <p>BMSCs-CM has anti-inflammatory and anti-oxidative properties. Administering BMSCs-CM serve as cell-free therapy to treat the SMSGs and kidney damage caused by Amiodarone toxicity.</p> Graphical Abstract <p>A diagram showing a graphical abstract for the present study.</p> <p></p>