Plants extracts were used in herbal medicine since ancient times owing to their therapeutic effectiveness, availability and accessibility in an experimental study. In the current study we used methanolic Lycium shawii extract (MLSE) investigate biological and medical active compounds by gas chromatography spectrometry (GC-MS) and evaluate its therapeutic ability against amikacin induced liver toxicity. 32 experimental male mice were divided into 4 groups; GI (negative control) was given Dimethyl sulfoxide (DMSO), GII was given amikacin (100mg/kg), group GIII was received (MLSE) alone, while group GIV was received both 100mg/kg of amikacin and 200 mg/kg of MLSE. GC-MS result showed 20 medicinally active compounds as shown in table 1. Most of these compounds reported as anti-inflammatory, antioxidant, anti-apoptotic and even anti-cancer. The biochemical tests revealed significant P≤ 0.05 therapeutic potential of MLSE in GIV to normalize the disturbance in the liver enzymes values (ALT, AST and ALP) that induced by amikacin in GII compared with GI. Additionally, histopathological study was illustrated that MLSE exhibit potent role in GIV in reduction amikacin-induced hepatotoxicity in GII compared with normal control GI. Collectively the MLSE play an important role in overcoming and suppression of amikacin hepatotoxicity. According to above results we recommended that Lycium shawii extract can use in medical and pharmaceutical field after further clinical and genetic evaluation for its safety and activity.