Sphingolipids (SLs) are common in all eukaryotes, prokaryotes, and viruses, and played a vital role in human health. They are involved in physiological processes, including intracellular transport, cell division, and signal transduction. However, there are limited reviews on dietary effects on endogenous SLs metabolism and further on human health. Various dietary conditions, including the SLs-enriched diet, high-fat diet, and vitamins, can change the level of endogenous SLs metabolites and even affect human health. This review systematically summarizes the main known SLs in foods concerning their variety and contents, as well as their isolation and identification approaches. Moreover, the present review discusses the role of dietary (particularly SLs-enriched diet, high-fat diet, and vitamins) in endogenous SLs metabolism, highlighting how exogenous SLs are digested and absorbed. The role of SLs family in the pathogenesis of diseases, including cancers, neurological disorders, infectious and inflammatory diseases, and cardiovascular diseases, and in recently coronavirus disease-19 outbreak was also discussed. In the post-epidemic era, we believe that the concern for health and the need for plant-based products will increase. Therefore, a need for research on the absorption and metabolism pathway of SLs (especially plant-derived SLs) and their bioavailability is necessary. Moreover, the effects of storage treatment and processing on the content and composition of SLs in food are worth exploring. Further studies should also be conducted on the dose-response of SLs on human health to support the development of SLs supplements. More importantly, new approaches, such as, making SLs based hydrogels can effectively achieve sustained release and targeted therapies.