Background: In Little Andaman Island, Onges is one of the particularly vulnerable Tribal Groups settled in Dugong Creek, whereas the Nicobarese tribe resides at Harminder Bay village. Having abode in the vicinity of the forest, a strong ethnobotanical practice prevails in this Island since ancient time. Objectives: This study was an attempt to document the medicinal plants used in this Island, with a view to preserve the ethnobotanical knowledge and to protect the biodiversity of this area. Materials and Methods: Fieldwork was conducted during December 2012 and December 2014. Data were collected through interview, questionnaire, and group discussion with traditional knowledge practitioners residing in the study site. Data were analyzed to determine the informant consensus factor (ICF), family use value, and UV of the plants. Results: The study documented 42 medicinal plant species belonging to 26 families, which are used for the treatment of at least 25 different ailments. The highest ICF value (0.64) was observed for injuries and trauma. Euphorbiaceae family constituted the highest number of plant species. Plants with the highest UVs were Ocimum tenuiflorum L., Morinda citrifolia L., Zingiber squarrosum Roxb., and Eupatorium odoratum L. The most common growth form observed were shrubs (33.33%). Leaves were found to be the most frequently used plant part. Conclusions: The present study revealed the use of few endemic plants, extensively for medicinal preparation, demonstrating an effective ethnobotanical practice in the study area. In future, these plants can be subjected to bioassay-guided investigation, while other plants can be screened for their bioactivity, to determine their medicinal property.