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Cytogenetic analysis is essential to determine the effect of mutagens and antimutagens on genetic material. This study was done to evaluate the protective effect of root bark extract of <i>Morus alba</i> (<i>M. alba</i>) against cyclophosphamide induced somatic and germinal cell damage in male rats. The ethanolic extract of <i>M. alba</i> (0.25, 0.5 and 1 g/kg, 2 weeks) was evaluated against cyclophosphamide (75 mg/kg, single dose) induced nuclear damage. The sampling was done after 48 h of the clastogen treatment. The somatic and germinal nuclear damage was studied by bone marrow micronucleus and sperm analysis, respectively. Serum superoxide and catalase levels were estimated to determine the antioxidant status in each group. The results were analyzed statistically to find the significant variation. The administration of <i>M. alba</i> for 2 weeks suppressed dose-dependently the changes induced by cyclophosphamide. <i>M. alba</i> (0.5 g/kg) decreased the frequency of micronucleated erythrocyte, sperm shape abnormality and enhanced the sperm count, sperm motility and polychromatic-normochromatic erythrocytes ratio significantly (<i>p</i> < 0.05) in comparison with the cyclophosphamide treated group. The highest tested dose of <i>M. alba</i> (1 g/kg) produced more prominent suppression (<i>p</i> < 0.01) in the cyclophosphamide-induced somatic and germinal cell defects. The results also showed significant (<i>p</i> < 0.05) improvement in the serum antioxidant enzymes levels with <i>M. alba</i> when compared with the challenge group. The lower dose of <i>M. alba</i> extract (0.25 g/kg) prevented the CP-induced changes but was found to be statistically insignificant. Therefore, antimutagenic potential of the high dose of the extract of <i>M. alba</i> is possibly due to its antioxidant nature. The ability of the <i>M. alba</i> extract to prevent the nuclear damage could play an important role in overcoming several mutational defects that are associated with anticancer chemotherapy.