There has been considerable interest in dietary supplements in the last two decades. Companies are releasing new specifics at an alarming pace, while dietary supplements are one of the less-studied substances released for public consumption. However, access to state-of-the-art and high-throughput techniques, such as the ones used in omics, make it possible to check the impact of a substance on human transcriptome or proteome and provide answers to whether its use is reasonable and beneficial. In this review, the main domains of omics are briefly introduced. The review focuses on the three most widely used omics techniques: NGS, LC-MS, NMR, and their usefulness in studying dietary supplements. Examples of studies are described for some of the most commonly supplemented substances, such as vitamins: D, E, A, and plant extracts: resveratrol, green tea, ginseng, and curcumin extract. Techniques used in omics have proven to be useful in studying dietary supplements. NGS techniques are helpful in identifying pathways that change upon supplementation and determining polymorphisms or conditions that qualify for the necessity of a given supplementation. LC-MS techniques are used to establish the serum content of supplemented a compound and its effects on metabolites. Both LC-MS and NMR help establish the actual composition of a compound, its primary and secondary metabolites, and its potential toxicity. Moreover, NMR techniques determine what conditions affect the effectiveness of supplementation.