The aim of this study was to investigate the protective effect of L-carnitine (L-CAR) in tamoxifen (TAM)–induced toxicity and antitumor activity.Adult female rats were randomly divided into 4 groups. Group I was served as control, groups II and III were injected with (10mg/kg, P.O) TAM and L-CAR (300 mg /kg, i.p.) respectively while, group IV was treated with both compounds.The treatment continued daily for 28 days. Administration of TAM resulted in significant increase in serum lipid profiles, liver enzymes and bilirubin level. In addition, TAM produced significant increase in lipid peroxides (LPO) level accompanied with significant decrease in superoxide dismutase (SOD) activity of hepatic and uterus tissues and significant decrease in glutathione (GSH) content of uterus tissue. Administration of L-CAR prior to TAM treatment decreased significantly serum lipids and liver enzymes and significantly increased SOD activity in liver and uterus tissues compared to TAM treated group. Furthermore, it restored LPO and GSH levels in uterus tissue. On the other hand, the apoptotic markers of caspases 9 and 3 were not detected in liver of all the treated groups. Histopathologically, alterations in the liver and uterus structures after TAM treatment which was attenuated by L-CAR administration. The antitumor effect and survival of the combined treatment of Ehrlich Ascites Carcinoma (EAC)-bearing mice was less than each one alone. In addition, L-CAR interestingly increased survival rate of EAC-bearing mice more than TAM treated group. In conclusion, L-CAR has beneficial effects regarding TAM toxicity; however, it interferes with its antitumor effect.