Nelumbo nucifera, or sacred lotus, has been valuable for us to use as vegetable, functional food, and herb medicine for over 2,000 years. The purpose of this article is to systematically review the traditional/ modern uses, chemical compositions and pharmacological activities on different parts of N. nucifera. Traditionally, this plant has been used to treat chronic dyspepsia, hematuria, insomnia, nervous disorders, cardiovascular diseases, and hyperlipidemia. Now, phytochemical investigations on different parts of N. nucifera have indicated a wide spectrum of at least 255 constituents belonging to different chemical groups, including proteins, amino acids, polysaccharides, starch, flavonoids, alkaloids, essential oils, triterpenoids, steroids, and glycosides. Meanwhile, its pharmacological activities, including anti-obesity, antioxidant, anti-inflammatory, cardiovascular, hepatoprotective, hypoglycemic, hypolipidemic, antitumor, memory-improving and antiviral activities, have also been reviewed, together with its applications in health food industry and clinic uses of its single plant or herbal formulae. Herein, this review will provide state-of-the-art overview on its traditional and modern uses in food industry and medicines, together with the comprehensive profiles of phytochemicals, and health promoting bioactivities of this valuable plant. In addition, the new perspectives and future challenges in the research on lotus are also outlined.