Ganoderma lucidum has received a lot of attention recently due to its medicinal potential activities. The aim of this designed experiment was to evaluate the beneficial effects of Ganoderma lucidum extract against lithium carbonate induced testicular toxicity and related lesions in mice testis. For this purpose, lithium carbonate at a dose of 30 mg/kg, followed by 75, 150 mg/kg Ganoderma lucidum extract orally were administered for 35 days. The results were obtained from Ganoderma lucidum extract analysis prove contained a large amount of polysaccharides, triterpenoids and poly phenols based on spectrophotometric assay. Also, DPPH assay for Ganoderma lucidum extract showed high level of radical scavenging activity. The hematoxylin & eosin cross section from lithium carbonate treated group exhibited significant alterations in seminiferous tubules. Moreover, lithium carbonate induced oxidative stress via lipid peroxidation and generate MDA (P < 0.001). In addition, lithium carbonate initiated germ cells apoptosis via increase Bax expression (p < 0.001) and reduce germ cells differentiation through down-regulation of c-Kit expression (p < 0.05). Results from CASA showed that sperm parameters like count, motility and viability significantly decreased in lithium treated group (p < 0.001). It is clear that lithium carbonate induce severe damage on male reproductive system and histopathological damages via generation oxidative stress but supplementation with Ganoderma lucidum extract exhibited prevention effects and repaired induced damages.