This study was purposed to explore the synergistic amelioration effect and optimal feeding time of sesame oil and squalene on hyperlipemia-induced sexual dysfunction rats. We established the hyperlipidemia-induced reproductive damage model, the three groups of test substances (sesame oil, a mixture of sesame oil and squalene, and sildenafil) were orally administrated to those hyperlipidemic rats on day 30 and day 60. The results showed that compared with the pure sesame oil, the mixture of sesame oil and squalene can synergistically decrease concentration levels of TG, TC, and LDL-C, significantly increasing the serum testosterone level and sperm count of the epididymal tail, which the 30 days’ effect was better than the day 60. Compared with the model control (MC) group, the Organ Coefficient of penile increased significantly in the sesame oil (SO), sesame oil+ Squalene (SOS), and Sildenafil (SN) group, and no pathological changes were found in the penile and testis in above three groups at the day 30 and the day 60. In conclusion, the present results demonstrated that sesame oil and squalene have a synergistic amelioration effect on lowering blood lipid and promoting the recovery of erectile and sexual function on hyperlipemia-induced reproductive damage rats at day 30. However, further studies should be carried out to deeply elucidate the molecular mechanisms of Sesame oil and squalene in lowering blood lipids and improving sexual function in vivo.