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