Background: Phytochemicals and their derivatives/analogues represent over 50% of the current medicines worldwide in clinical use. Despite a significant contribution to the total bioactive natural plant products, aquatic plants are underestimated, and several species are extinct and in the endangered list. Objective: The aim of this review article is to draw the attention of common people and scientists toward a few important contributions of the aquatic plants to natural product chemistry and drug discovery by highlighting the chemical and pharmaceutical aspects of the same. Methods: The presented data were collected and selected from the literature obtained by an online search for the ethnomedicinal properties, biological activities and bioactive chemical constituents of aquatic plants using Google Scholar, PubMed and Scifinder chemical abstract service. Results: The selected literature data revealed that the extract and compounds isolated from several aquatic plants possess significant biological/pharmaceutical properties. For example, the α-asarone (24) and asiatic acid (33) isolated from Acorus calamus and Centella asiatica, respectively, exhibited significant neuroprotective effects in vitro and in vivo. The cripowellin A (59), cripowellin C (60), cripowellin B (61) and cripowellin D (62), isolated from Crinum erubescens, exhibited potent antiplasmodial and antiproliferative activities with half maximal inhibitory concentration (IC50) in nanomolar range (11-260 nM). Several other alkaloids from different Crinum species have also shown anticancer properties against different cancer cell lines with IC50 value <5 µM. Alkaloids and resin glycosides, isolated from different Ipomoea species, have displayed significant psychotropic, psychotomimetic, anticancer, and antibacterial activities with IC50 value <5 µM. Conclusion: The aquatic plants play a significant role in the discovery of bioactive natural products. Although several biological activities and bioactive compounds have been reported from these plants, further assessment and scientific validation of most of their traditional usages still need to be done. There are several other similar species that are underestimated and not much explored. Many aquatic plants, such as Ipomoea carnea Jacq., Juncus lomatophyllus Spreng., Commelina benghalensis Linn, Gunnera perpensa L., Scirpus maritimus L. and Mentha longifolia (L.) L., may be considered for further evaluation. In addition to these, one should not undermine the potential of Crinum macowanii for COVID-19 pathogenesis, as its chemical constituent lycorine has shown significant SARS-CoV-2 inhibitory potential (EC50, 0.3 μM; SI >129). Furthermore, most rural communities are still using the wetland resources for their cultural, medicinal, economic, domestic, and agricultural needs. Hence, the conservation of aquatic plants and wetlands is an issue of great concern. © 2023 Bentham Science Publishers.