Cyclophosphamide (CP) is one of the most popular alkylating anticancer drugs that show a high therapeutic index, despite the widespread side effects and toxicity particularly in high-dose regimens and long-term use. Here, we evaluated and compared the efficacy of two different doses (50 and 100 mg/kg body weight, given orally for 30 consecutive days) of Egyptian sweet marjoram leaf powder (MLP) and marjoram leaf aqueous extract (MLE) in alleviating the genotoxicity, immunosuppression and other complications induced by CP in non-tumour-bearing albino rats. The present study showed (probably for the first time) that both MLP and MLE significantly alleviated (P < 0·05–0·001) most side effects and toxicity of CP-treated rats including the increase in chromosomal aberrations of bone marrow cells and serum malondialdehyde level, the decrease in the level of serum Ig, the delayed type of hypersensitivity response as also the weights and cellularity of lymphoid organs, and myelosuppression, leucopenia, macrocytic normochromic anaemia as well as thrombocytopenia by reactivating the non-enzymic (reduced glutathione) and enzymic (catalase, glutathione peroxidase, glutathione S-transferase, superoxide dismutase) antioxidant system and increasing the mitotic index of bone marrow cells. The modulatory effects of marjoram leaves shown in the present study were dose dependent in most cases and much higher in MLE (21–23 % for all parameters taken together). In addition, the doses used in the present study were considered safe. In conclusion, sweet marjoram leaves (especially in the form of a herbal tea) may be useful as an immunostimulant and in reducing genotoxicity in patients under chemotherapeutic interventions.