The therapeutic effects of alpha lipoic acid (LA) and metformin (MET) against the myocardial complications associated with hypothyroidism were assessed in the current study. Rats were divided into three groups: control, hypothyroidism model induced by propylthiouracil (PTU), hypothyroidism model treated with LA and/or MET. At the end of the experiment, the thyroid hormones (T3, T4 and TSH) were measured in the serum. Lipid peroxidation (MDA), nitric oxide (NO), reduced glutathione (GSH), NrF2, BCL2, NF-κB, serotonin (5-HT), norepinephrine (NE) and dopamine (DA), acetylcholinesterase (AchE), monoamine oxidase (MAO) and Na+,K+,ATPase were measured in the cardiac tissue. The histopathological changes were also examined. PTU significantly decreased T3 and T4 and significantly increased TSH. A significant increase in MDA, GSH, NrF2, BCL2, NF-κB, 5-HT, NE, DA, AchE, MAO and Na+,K+,ATPase and a significant decrease in NO were observed in the cardiac tissue of hypothyroidism model. This was associated with histopathological changes. LA alone or with MET restored T3 and TSH and improved almost all the biochemical changes except the decreased NO and the increased DA in the cardiac tissue. MET restored T3, T4 and TSH and the biochemical changes induced in the cardiac tissue. MET ameliorated the histopathological changes that were still observed with LA alone or in combination with MET. The present findings indicate that MET had cardioprotective effect against hypothyroidism and its myocardial complications. This effect was less prominent with LA alone or in combination with MET. No synergistic effect was observed between LA and MET.