Introduction: Adiantum nelumboides (Adiantum) is an endangered fern with a narrow distribution along the Yangtze River in China. Due to its cliff-dwelling habit, it experiences water stress conditions, which further endangers its survival. However, no information is available about its molecular responses to drought and half-waterlogging conditions. Methods: Here, we applied five and ten days of half-waterlogging stress, five days of drought stress, and rewatering after five days of drought stress, and studied the resulting metabolome profiles and transcriptome signatures of Adiantum leaves. Results and Discussion: The metabolome profiling detected 864 metabolites. The drought and half-waterlogging stress induced up-accumulation of primary and secondary metabolites including amino acids and derivatives, nucleotides and derivatives, flavonoids, alkaloids, and phenolic acid accumulation in Adiantum leaves. Whereas, rewatering the drought-stressed seedlings reversed most of these metabolic changes. Transcriptome sequencing confirmed the differential metabolite profiles, where the genes enriched in pathways associated with these metabolites showed similar expression patterns. Overall, the half-waterlogging stress for 10 days induced large-scale metabolic and transcriptomic changes compared to half-waterlogging stress for 05 days, drought stress for 05 days or rewatering for 05 days. Conclusion: This pioneering attempt provides a detailed understanding of molecular responses of Adiantum leaves to drought and half-waterlogging stresses and rewater conditions. This study also provides useful clues for the genetic improvement of Adiantum for drought/half-waterlogging stress tolerance. CI - Copyright (c) 2023 Liang, Dun, Li, Ma, Zhang, Su and Wu.