This study investigated the ameliorative effect of aqueous crude extract of the aerial parts of Leonurus cardiaca on doxorubicin-induced cardiovascular damage in Wistar rats. Aqueous crude extract of Leonurus cardiaca was prepared based on standard Laboratory condition. A total of 55 male and female rats weighing between 170 ± 15 and 180±15g were used for this study. The rats were grouped into 11 groups of five rats per group. Group 1 and 2 served as normal and negative control rats respectively. Rats in group 3-11 were intraperitoneally administered 18mg/kg of doxorubicin once and were treated with the crude extract at 166, 250, and 500mg/kg for 7, 14, and 21 days. All biochemical, hematological, and histological analyses were carried out based on standard methods. The mean plasma troponin T and I, IL-6 and C-reactive protein concentrations of the negative control were 357.93±0.01 pg/mL, 241.51±0.00 pg/mL, 63.94±0.01 pg/dl, and 41.03±0.01 mg/ml respectively. The plasma troponin T and I, IL-6 and C-reactive protein concentrations treated for 21 days were 270.32±0.01 pg/mL, 217.84±0.01 pg/mL, 42.75±0.01 pg/dl, and 18.03±0.01 mg/ml respectively. The mean MDA, GSH concentrations, GPx, CAT and SOD activities in doxorubicin-induced cardiovascular damage rats, treated with the extract at 500mg/kg were 5.01±0.01mmol/l, 68.46±0.02µg/mg.protein, 70.21±0.01mg/pro.min, 141.62±1.80IU/g, and 19.05±0.02mg/g respectively and were significantly different from those of group 2. Aqueous crude extract of Leonurus cardiaca at 500mg/kg ameliorated the damage induced by doxorubicin on the heart tissues, hence could serve as a novel herbal agent for the treatment of cardiovascular damage.