Antigenotoxic properties of many medicinal plants have been widely recognized and some of them have been commercially exploited. Plant derived antioxidants play a very important role in alleviating problems related to oxidative stress. Therefore, the present study was aimed at assessing the protective effect of the medicinal plant Costus speciosus against genotoxicity and histopathological alterations of streptozotocin (STZ)-induced diabetes mellitus in male rats. Animals were divided into 8 groups (10 animals/group) as follows: 1) Streptozotocin (ip single dose of 50 mg/kg bw STZ , 3 d after the blood sugar was 200-250 mg/dl); 2) STZ + insulin (1 U for 14 days starting from d3 after STZ injection); 3) STZ + 50 mg/kg bw costus (oral administration); 4) STZ + 100 mg/kg bw costus; 5) STZ + 150 mg/kg bw costus; 6) STZ + 50 mg/kg bw nanocostus (oral administration); 7) STZ + 100 mg/kg bw nan ocostus; 8) STZ + 150 mg/kg bw nanocostus. Beside the control group (Citrate buffer). The results of the present study revealed that the treatment with STZ induced high frequency of micronuclei, DNA damage, chromosomal aberrations and histopathological changes. However, costus or nanocostus treatment reduced all these parameters especially with 50 mg/kg between nanocostus. This study proved that treatment with C. speciosus has a strong inhibitory effect against the genotoxicity and histopathologic alterations induced by STZ. In conclusion, these results strongly suggest that the extract of Costus speciosus might be anti-genotoxic, and anti-histopathologic agent.