Background: Streptococcus mitis (S. mitis) belongs to the viridan streptococci group which is rarely isolated as a causative pathogen of corneal ulcer. When it causes keratitis, penetrating keratoplasty (PK) might be necessary. Herein, we demonstrated amniotic membrane transplantation (AMT) can be an easier surgery with acceptable outcomes and less complication. Case presentation: A 63-year-old female Taiwanese presented with right persistent corneal ulcer for nine months. Culture from corneal scraping yielded S. mitis. A right eye descemetocele decreased from 3 mm in diameter to 0.8 mm after continuous administration of topical Vancomycin and Ceftriaxone for two weeks. Due to retarded healing, AMT was performed. Her corneal erosion healed and became clear gradually. Her visual acuity recovered from counting fingers initially to 20/200 finally 17 months after AMT. Conclusion: This unusual case illustrated that antibiotics plus AMT instead of PK may be an effective alternative treatment to promote epithelialization and reduce inflammation in corneas complicated by S. mitis keratitis.