Gastric cryptosporidiosis (GC) is an insidious infection in squamates caused by the protozoan Cryptosporidium serpentis and has impacted the captive breeding colony for the eastern indigo snake (Drymarchon couperi; EIS) reintroduction program. This study investigates a novel treatment of GC in EIS. Seventeen EIS with GC were randomly divided into three groups: A, B, and C. Group A (n = 6) received parenteral administration of 25 mg/kg vitamin C, 0.5 mg/kg vitamin E, and 50 μg/kg selenium and 5 ml/kg 3 % H2O2 gavage; Group B (n = 6) received the same injections but 5 ml/kg water gavage; and Group C received no treatments and served as controls. All EIS from Groups A and B tested negative for C. serpentis for three months following treatment, while only 60% (3/5) in Group C tested negative. EIS testing negative received one 4 mg/kg dexamethasone sodium-phosphate injection. For three months following dexamethasone, 66.7% (4/6) in Group A continued to test negative compared to 83.3% (5/6) in Group B and 20% (1/5) in Group C. EIS testing negative underwent gastric biopsies but only one from Group C was confirmed to be negative for C. serpentis. Although parenteral vitamin C, vitamin E, and selenium with H2O2 gavage decreased shedding of C. serpentis, it did not outperform the vitamins/selenium without H2O2. The parenteral use of 25 mg/kg vitamin C, 0.5 mg/kg vitamin E, and 50 ug/kg selenium once weekly cannot be recommended for treatment of C. serpentis in EIS if complete resolution of the parasite is desired.