Clomipramine (Clm.) is considered one of the most effective tricyclic antidepressant drugs. The present study focuses on the ability of the flavonoid extract of tiger nuts to reduce the damage caused by the drug. The study involved 48 male mice weighing 30 g ± 5 and divided into four groups of 12 mice for each group. The control group with no treatment, the G2 group treated with 200 mg/kg of flavonoid extract, and G3 treated with 50 mg of Clm. and the G4 group was treated with 50 mg Clm. + 200 mg/kg of extract. The treatment continues for 40 days. The results showed a significant (P < 0.05) increase in FSH, LH, and testosterone T, and in addition, an increase in semen quality and the sperm abnormalities decreased significantly (P < 0.01) in the G2 group, while the G3 group showed a significant (P < 0.01) decrease in hormone levels (FSH, LH, and T) and a decrease in sperm count and motility and an increase in sperm abnormalities compared to the control group. The G4 showed a significant (P < 0.01) increase in FSH, with no significant effect on LH levels, in addition to a decrease in T levels; also, there was an increase in dead sperm with a reduction in sperm motility and an increase in sperm abnormalities compared to the control group. The histological study displays a disruption in spermatogenesis, an interruption in sperm development, dense infiltration of inflammatory cells in the interstitial space between seminiferous tubules, tubular atrophy, and bleeding seen within or around seminiferous tubules in the Clm. group, while the damage is reduced in the G4 group. This indicates that C. esculentus improves testicular and sex hormonal function