Background:  Calcium sennosides are the main active metabolites of sennas, which have a powerful interest to phytochemical and pharmacological research, due to their brilliant medicinal values. It is well known in folk medicine for their laxative and purgative uses.  Materials and Methods: This experiment aimed to assess cytogenetic (micronucleus assay and chromosomal aberration study) and biochemical effects of calcium sennosides at a working dose (24 or 48 mg/ ml) on suppressing radiation hazards in human blood cultures. Biochemical investigations include superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), cyclooxygenase-2 (COX-2) and lactate dehydrogenase (LDH) levels. The treatment periods were 48 and 72 hrs post-irradiation at a dose of 3 Gy. Triple blood cultures for each blood sample were set up.  Results: Ionizing radiation exposure induced significant increase in micronuclei (MN) frequencies in both mono- and bi- nucleated cells, and all types of chromosome aberrations, beside significant decrease in SOD and CAT activities. While TNF-α, IL-8, COX-2 and LDH levels were significantly increased after irradiation. Treatment with calcium sennosides exhibited decreased of micronuclei and chromosome aberration numbers and enhancement in the level of SOD and CAT activities. In addition, a significant amelioration in IL-8, TNF-α, COX-2 levels and LDH activity were scored. Conclusion: Present results revealed the antimutagenic and the anti-inflammatory effects of sennosides against oxidative stress induced by γ- irradiation.