Introduction: Cyclophosphamide (CP) is a widely used anti-cancer drug which can induce serious male infertility. Aim of the study: The present study aims at determining the protective role of alpha-lipoic acid and royal jelly in improving biochemical, histological and ultrastructural disorders in the testis of rats induced by CP. Materials and Methods: 64 rats were separated into eight groups each of 8 rats. (G1) control group, (G2) alkaline solution treated group, (G3) DMSO treated group, (G4) Alpha-lipoic acid (LA) treated group, (G5) Royal jelly (RJ) treated group, (G6) CP treated group (5 mg/kg b.wt) three days per a week for 4 weeks, (G7) CP plus LA treated group (25 mg/kg b. wt) and (G8) CP plus RJ treated group (1g/kg b. wt). Animals were sacrificed after 4 weeks. Results: CP leads to an increase in lipid peroxidation in form of malonaldehyde (MDA) and decline in superoxide dismutase (SOD) in comparison with control. It caused histopathological changes in testes of rats including vacuolation, exfoliation of germ cells in the lumina of the seminiferous tubules, and maturation arrest. Furthermore, oedema was also observed and congestion of the intertubular blood vessels. Ultrastructurally, the boundary tissue of some tubules displayed noticeable changes; it was thickened and folded. Sertoli cells displayed an increase in the number of lysosomes and their nuclei showed signs of pyknosis, cytoplasmic vacuolation. Administration of LA and RJ to CP-treated rats revealed marked improvement in the altered level of SOD and MDA activities when compared with the CP-treated group and showed improvement in histopathology and ultrastructure of the testis. Conclusion: Treatment of the cyclophosphamide with the alpha-lipoic acid-induced great regaining of the damaged testicular tissues and royal jelly induced little regaining of the damaged testicular tissues, so LA was effective in treatment with CP than RJ with CP. This enhancement because of their antioxidant properties and its scavenging abilities against active free radicals.