The use of doxorubicin (DOX) as an anti-cancer agent might cause side effects to other organs suchas testicle due to increased oxidative stress. This study was aimed to investigate the antioxidant effect ofmangiferin inside Mangifera indica for lowering testicle toxicity. A total of 24 sprague dawley male rats wasdivided into 4 groups. The normal group was injected with 0.9% of NaCl, the negative control group receivedDOX with dosage of 15 mg/BW while DOX treated group received mangiferin with dosage of 30 mg/BW and60 mg/BW. After 7 weeks, all rats were killed and testicles from every rats were subsequently collected foroxidative stress parameter analysis which were measuring the rate of malonedyaldehide (MDA), superoxidedysmutase activity, histological changes, and apoptosis of caspase-9 and caspase-12. Administration ofmangiferin with dosage of 30 mg/BW and 60 mg/BW for 7 weeks decreased the destruction of spermatogeniccells and sertoli cells of seminiferous tubule, decreased the rate of MDA, and lowered the expression ofcaspase-9 in the group which received DOX and mangiferin. Improvement in those parameters indicated thatmangiferin had a protective effect towards spermatogenic and sertoli cells of seminiferous tubule destructionin rats which were given DOX.