Waterlogging is becoming a critical threat to plants growing in areas prone to flooding. Some plants adapt various morphological and biochemical alterations which are regulated transcriptionally to cope with the situation. A comparative study of waterlogging response in two different varieties of Mentha namely Mentha piperita and Mentha arvensis was performed. M. arvensis showed better response towards waterlogging in comparison to M. piperita. M. arvensis maintained a healthy posture by utilizing its carbohydrate content; also, it showed a flourished vegetative growth under waterlogged condition. Soluble protein, chlorophyll content, relative water content, and nitric oxide scavenging activity were comparatively more salient in M. arvensis during this hypoxia treatment. Lipid peroxidation was less in M. arvensis. M. arvensis also showed vigorous outgrowth of adventitious roots to assist waterlogging tolerance. To further investigate the possible gene transcripts involved in this response, we did cDNA subtraction of waterlogging treated M. piperita and M. arvensis seedlings. cDNA subtraction has identified thirty seven novel putative Expressed Sequence Tags which were further classified functionally. Functional classification revealed that maximum percentage of proteins belonged to hypothetical proteins followed by proteins involved in biosynthesis. Some of the identified ESTs were further quantified for their induced expression in M. arvensis in comparison to M. piperita through quantitative real-time PCR.