<p>Di-n-butyl phthalate (DBP), an environmental endocrine disruptor, can induce male reproductive dysfunction. In the study, the protective mechanism of ginsenoside Rg3 (Rg3) against DBP-induced damage to spermatogenic function was explored through the Nrf2/antioxidant response element (ARE) signaling pathway in mice. The protective effects of Rg3 were analyzed by comparing the quality of sperm, the levels of reproductive hormones and the mRNA and protein expression of Nrf2, NQO1, and StAR in the testicular tissue. The results showed that Rg3 restored the reproductive damage caused by DBP, improved the thesticular structure, enhanced the number and motility of sperm, and upregulated the mRNA expression levels of Nrf2, NQO1, StAR and increased the phosphorylation of proteins in testicular tissue. Ginsenoside Rg3 can activate the Nrf2/ARE pathway, upregulate NQO1, regulate StAR protein expression, and has a relieving effect on DBP-induced reproductive dysfunction in mice. Rg3 may become a potential therapeutic drug for male infertility due to environmental toxicants.</p>