Doxorubicin (DOX) is a commonly used chemotherapeutic agent for the treatment of different solid and non-solid cancers. However, it does have limited application due to its remarkable cardiotoxicity. The mechanism of DOX-induced cardiotoxicity is still controversial. The major current theories include the production of reactive oxygen species (ROS), cellular mitochondria dysfunction, apoptosis, and autophagy dysregulation. Meanwhile, two candidates of the insulin sensitizer group, metformin (MET) and BGP-15, have been demonstrated with cardioprotective effects. In our study, we investigated such effects on the DOX-treated rats by using the measured heart functions, lipidperoxidation level in group of rats given DOX alone versus those pretreated with MET and BGP-15. In our experiment, 24 adult 250-300g rats, were randomly divided into four groups as (i) control group – received only saline in a 10-day oral treatment and a followed 10-day intraperitoneal treatment; (ii) DOX group – received a 10-day oral treatment with saline and followed by a 10-day intraperitoneal treatment with DOX (1 mg/kg-dosage/day) alone; (iii) MET group – received a 10-day oral treatment with MET (250 mg/kg-dosage/day) alone and followed by a 10-day combination treatment of oral MET and intraperitoneal DOX (above mentioned doses); and (iv) BGP-15 group – received a 10-day oral treatment with BGP-15 (25 mg/kg-dosage/day) alone and followed by a 10-day combination treatment of oral BGP-15 and intraperitoneal DOX (above mentioned doses). The rats were sacrificed after 72 hours since the last treatment. The heart functions were immediately measured under Langendorff apparatus. The heart tissues were then stored for lipidperoxidation assay. After evaluation, we found that the applied DOX treatment successfully induced cardiotoxicity. Both performed pretreatment slightly improved cardiac functions against DOX treated group. In case of BGP-15 group, the results showed significant increase in aortic flow. One limitation of the study is that each group contains only six animals. For further conclusions necessary to involve additional animals and perform other molecular biological experiment to investigate the underlying mechanisms.