Aim: Anthracycline-induced cardiotoxicity is the most common constraint of its use in the treatment of various types of cancer. This study aimed to investigate the benefits of the addition of the l-carnitine / silymarin to anthracycline chemotherapy in patients with breast cancer. Methods: 83 patients were recruited from Clinical Oncology Department, Tanta University, Egypt, then prospectively randomized to receive their anthracycline-containing therapeutic regimen, control group (n=33), or anthracycline plus l-carnitine, l-carnitine group (n=25), or anthracycline plus silymarin, silymarin group (n= 25). Blood samples were collected at the beginning and after 6 months to measure LDH, CK-MB, cTn I, Anticardiolipin IgG, Fe, ferritin, and TIBC and % of saturation. % EF was documented. Data were statistically analyzed by ANOVA and paired t-test. P Results: The addition of l-carnitine to anthracycline chemotherapy has a significantly improved EF% (P=0.003), Anticardiolipin IgG (P=0.001), ferritin (P=0.001), and TIBC (P=0.011). The supplementation with silymarin to anthracycline chemotherapy had a statistically significant decrease in Anticardiolipin IgG (P=0.000), iron (P=0.001), ferritin (P= 0.001), TIBC (P=0.007), and % saturation (P=0.001). Silymarin group showed a significant decrease in iron profile compared to the l-carnitine group. Conclusion: The co-administration of l-carnitine or silymarin with anthracycline chemotherapy represents a new therapeutic strategy for better control of anthracycline-induced cardiotoxicity. Silymarin resulted in more beneficial effects on the iron profile compared to l-carnitine with anthracycline or anthracycline chemotherapy alone.