Background <p>Soy-based diets are commonly used not only by humans but also by laboratory and domesticated animals. Recently, there has been much argument around soybeans and their products, mostly due to their phytoestrogen (PE) content. Intestinal microflora digests soybean isoflavones to produce estrogenic compounds such as genistein, daidzein, and equol, which can bind with estrogen receptors (ERs). In recent years, the consumption of soybean-formulated diets has increased significantly. Our study is designed to evaluate the effects of soybean-formulated diets exposure from perinatal to puberty on the fertility of male mice. </p> Methods <p>Thirty pregnant dams are classified into three groups: the control group (CG);soy-free group is fed on a casein-based diet, while the second and third groups are fed on diets containing 20% and 30% soy in both low and high soy groups(LSG and HSG), respectively, from gestational day (GD) 12 till postnatal day (PND) 21 (weaning day). Male offspring are isolated and fed on the same diet groups from PND 21 to 56 (killing day).</p> Results <p>Male mice fed on soy-based diets showed a significant reduction in body and testes weights, as well as reproductive performance. Additionally, there was a decrease in sperm count, viability, and motility, while sperm abnormalities increased. Serum total testosterone levels and total antioxidant capacities (TAC) also decreased. Conversely, levels of follicular-stimulating hormone (FSH) and luteinizing hormone (LH) increased, along with sperm DNA fragmentation. The diameters of seminiferous tubules and the heights of the seminiferous epithelium were reduced. Furthermore, the soy-based diet affected testicular histology.</p> Conclusions <p>These observations indicate that soybean-based diets during perinatal and postnatal exposures negatively impact male fertility.</p>