Aim: The aim of the study is to investigate the effect of Cynomorium songaricum (CS) on the damage caused by cyclophosphamide (CP) in SD rats. Methods: Rats with CP-induced oligoasthenospermia were treated with different concentration of CS. Testicle weight, epididymal sperm count (ESC), sperm motility, and serum testosterone were analyzed, and expression levels of Thy1, Oct4, PLZF, C-kit, and GDNF were detected in testis tissues. Transmission electron microscopy (TEM) was performed to observe the effect of CS on the spermatogenic damage by CP. Results: Compared with the CP group, there were significant differences in testicle weight, ESC, and sperm motility (p<0.05) observed in all concentrations of CS and CP+VitE groups (p<0.05). There were no significant differences in serum testosterone among the 6 groups (p>0.05). The qPCR results revealed a significant difference in Thy1, Oct4, PLZF and GDNF expression between the CP group and CS group (p <0.05), but there was no significant difference in C-kit between the two groups (p>0.05). The damage of CP was cured by CS observed under TEM. Conclusion: CS can increase sperm counts in the epididymis and improve sperm motility and has a therapeutic effect on the spermatogenic damage caused by CP in SD rats.