BACKGROUND/OBJECTIVES: Male hypogonadism is a condition where the body does not produce enough testosterone and significantly impacts health. Age, obesity, genetics, and oxidative stress are some physiological factors that may contribute to testosterone deficiency.Previous studies have shown many pharmacological benefits of Schisandra chinensis (S. chinensis) Baillon as an anti-inflammatory and antioxidant. However, the molecular mechanism of attenuating hypogonadism is yet to be well established. This research was undertaken to study the effects of S. chinensis extract (SCE) on testosterone deficiency.MATERIALS/METHODS: S. chinensis fruit was pulverized and extracted using 60% aqueous ethanol. HPLC analysis was performed to analyze and quantify the lignans of the SCE. RESULTS: The 2,2-diphenyl-2-picrylhydrazyl and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays confirmed that the SCE and its major lignans (schisandrol A and gomisin N) inhibit oxidative stress. Effects of SCE analysis on the testosterone level under oxidative stress conditions revealed that both schisandrol A and gomisin N were able to recover the lowered testosterone levels. Through mRNA expression of TM3 Leydig cell, we observed that the SCE lignans were able to induce the enzymes involved in testosterone biosynthesis-related genes such as 3β-HSD4 (P < 0.01 for SCE, and P < 0.001 for schisandrol A and gomisin N), 17β-HSD3 (P < 0.001 for SCE, schisandrol A and gomisin N), and 17, 20-desmolase (P < 0.01 for schisandrol A, and P < 0.001 for SCE and gomisin N). CONCLUSIONS These results support that SCE and its active components could be potential therapeutic agents for regulating and increasing testosterone production.