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Current study was planned to explore the therapeutic response of different doses of hydroethanolic extract of Epimedium grandiflorum leaves in male albino rats. Phytochemical analysis, HPLC and FTIR spectroscopy results revealed the presence of wide range of phenolic compounds and functional groups, respectively. Further, extract not induced significant hemolysis (7.56 ± 1.297%) against PBS (3.65 ± 0.35%) as negative control; while have significant clot lysis (44 ± 5.2%) potential, exhibited DPPH (78.87 ± 5.427%) scavenging, H 2 O 2 (31.82 ± 3.491%) scavenging, antioxidant and reducing power activities. In vivo experimentation in albino male rats’ revealed that administration of different doses (50, 100, 200 mg/Kg b.w.) of extract orally for 42 days after CCl 4 intoxication significantly (P < 0.05) restore the selected parameters including liver enzymes, renal profiles, and stress markers and significantly (P < 0.05) increased reproductive hormones like testosterone, luteinizing hormone, follicle stimulating hormone and prolactin while significantly (P < 0.05) decreased progesterone and estradiol toward normal in dose dependent manner. Significant (P < 0.05) improvement in the structural architecture of testicular tissue particularly in high dose group (200 mg/Kg b.w.) was also observed. Results revealed E. grandiflorum has significant therapeutic response to address the healthcare problems particularly of impotency.