The aim of this study was to evaluate the effect of Lepidium meyenii (maca) in chemically and physically subfertile mice. After 35 days, the following groups of mice were evaluated: control, sham, chemical subfertility, chemical subfertility–maca-supplemented, physical subfertility, physical subfertility–maca-supplemented and maca-supplemented only. Motility (32.36% ± 5.34%) and sperm count (44.4 ± 5.37 × 106/ml) in the chemically and physically subfertile mice (11.81% ± 4.06%, 17.34 ± 13.07 × 106/ml) decreased compared to the control (75.53% ± 2.97% and 57.4 ± 19.6 106/ml) and sham (53.5% ± 7.86% and 58.4 ± 14.10 106/ml). Maca was able to reverse the deleterious effect of motility (76.36 ± 1.97) as well as sperm count (53.5 ± 9.18 × 106/ml) on chemical subfertility. In contrast, maca did not reverse the effects of induced physical subfertility nor motility (18.78% ± 14.41%) or sperm count (20.17 ± 11.20 × 106/ml). The percentage of sperm DNA fragmentation in the physically subfertile mice increased (11.1% ± 19.29%) compared to the control (0.84% ± 0.85%). However, in the physically subfertile group, maca decreased sperm DNA fragmentation (2.29% ± 2.30%) closer to the sham (1.04% ± 0.62%) and the control (0.84% ± 0.85%). The group supplemented only with maca showed 0.54% ± 0.50% of spermatozoa with DNA fragmentation. Yet, the differences observed were statistically not significant. In conclusion, it appears that maca activates the cytochrome P450 system after chemically induced subfertility. However, it does not reverse the low mitochondrial membrane potential in spermatozoa compromised in the physical subfertility group.